와인덩굴 |
과일 |
에이치티씨티116 |
뉴멕시코 |
동결건조 |
히드록시신남산, 프로안토시아니딘, 스틸베노이드 |
세포주기 정지에 관여하는 스핑고지질 매개체인 디하이드로세라마이드 증가 및 증식속도 감소 |
(i) 세포주기 게이트키퍼 p53 및 p21 증가
(ii) 전사인자 Nrf2 활성화 |
[ 26 , 27 ] |
과일 |
카코-2 |
365mg/g |
메탄올 |
카테킨, 에피카테킨, 케르세틴, 갈산 |
항증식 활동 및 세포 사멸의 직접적 시작 |
G2/M 단계의 막힘 |
[ 28 , 29 ] |
씨앗 |
카코-2 |
10~ 25μg /mL |
물의 |
프로시아니딘 |
(i) 굴 깊이 증가
(ii) 세포 생존력 억제 및 조직학적 손상 점수 감소 |
감소된 MPO(골수과산화효소) 활동 |
[ 29 ] |
피부 |
뉴멕시코 |
7.5, 30, 60μg / mL |
메탄올 |
4'-게라닐옥시페룰산 |
뉴멕시코 |
뉴멕시코 |
[ 30 ] |
씨앗 |
대장암 줄기세포 |
6.25, 12.5, 25μg / mL |
뉴멕시코 |
(+)-카테킨, (−)-에피카테킨 |
뉴멕시코 |
(i) p53 증가, Bax/Bcl-2 비율 및 절단된 PARP
(ii) Wnt/ β -catenin 신호 전달 억제 |
[ 31 ] |
|
알리움 사티붐 |
뿌리 |
HT-29 |
20, 50, 100mg/mL |
에탄올 |
뉴멕시코 |
세포사멸 유도 및 세포주기 정지 |
(i) PI3K̸Akt 경로의 억제
(ii) PTEN의 상향 조절 및 Akt 및 p-Akt 발현의 하향 조절 |
[ 32 ] |
|
글리신 맥스 |
씨앗 |
카코-2, SW620, HT-29 |
12.5μg / mL |
물의 |
안토잔틴 |
세포 사멸 및 세포 밀도의 현저한 감소 |
Rab6 단백질 수치 향상 |
[ 33 ] |
씨앗 |
HT-29 |
240, 600ppm |
조잡한 |
사포닌 |
|
PKC 활성화 억제 및 알칼리성 인산가수분해효소 활성 증가 |
[ 33 ] |
씨앗 |
HT-29 |
뉴멕시코 |
조잡한 |
사포닌 |
뉴멕시코 |
(i) PMA 자극 세포에서 IκBα 분해 억제 (ii) COX-2 및 PKC 발현 다운레귤레이션 |
[ 34 ] |
|
카멜리아 시넨시스 |
잎 |
HT-29 |
0, 10, 30 , 50μM |
물의 |
카테킨, 에피갈로카테킨 갈레이트 |
종양세포 사멸 1.9배 증가, 내피세포 사멸 3배 증가 |
(i) ERK-1 및 ERK-2 활성화 억제
(ii) VEGF 발현 억제 |
[ 35 ] |
잎 |
카코-2, HT-29 |
300μM ( 마이크로 미터) |
물의 |
테아플라빈(TF-2T, F-3, TF-1) |
인간 대장암 세포 사멸 유도 |
NFκB , AP-1, CREB 및/또는 IL-6 의 조절 |
[ 36 ] |
잎 |
HT-29 |
68-80
0.73μg / mL |
뜨거운 물 추출 |
플라반-3-올(카테킨 & 타닌) & 폴리페놀(테아데놀 B) |
HT-29세포의 증식 억제 |
카스파제 3/7, 8 및 9의 발현 수준 증가 |
[ 35 ] |
|
유럽산 오일 |
과일 |
HT-29 |
150, 55.5
200 및 74 μmol /L |
메탄올과 클로로포름 |
마슬린산, 올레아놀산 |
항증식 활동 |
(i) 카스파아제 3 유사 활성이 6배로 증가
(ii) 미토콘드리아에서 슈퍼옥사이드 음이온 생성 |
[ 37 ] |
과일, 잎 |
SW480 및 HT-29 |
100~400m/z |
메탄올 및 헥산 |
올레산, 리놀레산, 감마-리놀렌산, 리그난, 플라보노이드, 세코이리도이드 |
두 세포주 모두에서 세포 성장 감소 |
(i) 제한된 G2M 세포주기
(ii) HT-29 세포에서 억제된 사이클로옥시게나제-2 발현 (iii) SW480 세포에서 β- 카테닌/TCF 신호전달
억제 (iv) subG1 단계로의 진입 촉진 |
[ 38 ] |
과일 |
카코-2 |
50μM ( 마이크로 미터) |
물의 |
페놀성 화합물, 진정한 하이드록실 티로솔(HT) |
Caco-2 세포의 증식 감소 |
CNR1 프로모터의 메틸화 수준 감소 |
[ 39 ] |
과일 |
HT115 |
25μg / mL |
하이드로에탄올 |
페놀성 화합물(p-히드록시페닐 에탄올, 피노레시놀 및 디히드록시페닐 에탄올) |
뉴멕시코 |
α5 및 β1 범위의 감소된 발현에 의한 억제 |
[ 40 ] |
올리브 공장 폐수 |
HT-29, HCT116, CT26 |
뉴멕시코 |
메탄올 |
하이드록시티로솔 |
(i) 억제된 증식
(ii) 억제된 이동 및 침입 |
(i) 새싹 형성 감소
(ii) VEGF 및 IL-8 수준 억제 |
[ 41 ] |
과일 |
카코-2 |
0~ 2,000μg /mL |
에탄올 |
티로솔, 하이드록시티로솔, 올레우로페인, 루틴, 케르세틴 및 루테올린과 아피게닌의 글루코사이드 형태 |
뉴멕시코 |
(i) S기에서 세포주기 정지 유도 |
[ 42 ] |
|
푸니카 그라나툼 |
주스 |
HT-29 |
50mg/L |
물의 |
엘라기탄닌, 푸니칼라진 |
암세포 증식 억제 |
(i) 억제된 TNFR 유도 COX-2 단백질 발현
(ii) p65 서브유닛의 인산화 감소 및 NF κ B 반응 요소 와의 결합 |
[ 43 ] |
씨앗 |
LS174 |
63.2μg / mL |
초임계유체 |
푸닉산, γ- 토코페롤, α- 토코페롤 |
세포독성 활동 |
(i) 길쭉한 세포체에서 세관 발달이 약간 감소함
(ii) 세포 연결 수 감소 |
[ 44 ] |
|
감초(Glycyrrhiza glabra) |
뿌리 |
HT-29 |
12.2 및 31μg / mL |
에탄올 |
리코칼콘 |
뉴멕시코 |
proapoptotic Bax의 단백질 수치 증가 |
[ 37 ] |
|
Opuntia fig-indica |
과일 |
카코-2 |
115μM ( 마이크로 미터) |
물의 |
베타라인 색소 인디카잔틴 |
증식하는 세포의 세포사멸 |
(i) 종양 억제 p16INK4a 유전자 프로모터의 탈메틸화
(ii) 침묵된 mRNA 발현 재활성화 및 p16INK4a 축적 |
[ 38 ] |
과일 |
HT-29 & Caco-2 & NIH 3 T3 (대조군) |
HT-29(4.9μg / mL) 대비 Caco-2(8.2μg / mL) |
NaOH를 이용한 알칼리 가수분해 |
이소람네틴 글리코사이드(IG5 및 IG6)-페놀 |
세포사멸과 괴사를 통한 세포사멸 |
카스파아제 3/7의 활성 증가 |
[ 45 ] |
|
파이퍼 베틀 |
잎 |
HT-29 및 HCT116 |
200.0μg / mL |
물의 |
하이드록시차비콜 |
항산화 능력과 더 큰 세포사멸 효과 유도 |
(i) 청소 활동
(ii) 친전자성 대사산물 형성 |
[ 41 , 46 ] |
|
프라가리아×아나나사 |
과일 |
HT-29 |
0.025, 0.05, 0.25, 0.5% |
에탄올 |
아스코르브산, 엘라그산 |
HT-29 세포의 증식 감소 |
8OHA 수치 증가, 8OHG 수치 감소 |
[ 40 ] |
|
이제 quelpaertensis |
잎 |
HT-29 HCT116 |
0, 100, 200, 300mg/L |
에탄올 |
p-쿠마르산, 트리신 |
억제된 집락 형성 |
비부착성 구형 형성은 CD133+ 및 CD44+ 집단을 억제합니다. |
[ 41 ] |
|
살비아 치넨시스 |
줄기 |
HCT116, 콜로라도 205 |
10, 20, 40, 60, 80, 100mg/L |
폴리페놀 |
테르페노이드, 페놀산, 플라보노이드, 디벤질사이클로옥타디엔 |
세포사멸 및 미토콘드리아 막 손실 |
유도된 G0/G1 세포주기 |
[ 42 ] |
|
루부스 이데우스 L. |
과일 |
HT-29, HT-115, 카코-2 |
3.125, 6.25, 12.5, 25, 50mg/L |
아세테이트 |
폴리페놀, 안토시아닌, 엘라기탄닌 |
뉴멕시코 |
G1기 세포수 감소 |
[ 47 ] |
로보 |
50 μL (50 μL ) |
물의 |
뉴멕시코 |
LoVo의 증식 억제 |
NFκB 경로 억제 |
[ 48 ] |
|
강황은 길어요 |
뿌리 |
HT-29, HCT15, DLD1, HCT116 |
(i) 단기 분석: 10배 희석 4회(100~0.1mg/L)
(ii) 장기 분석: 5, 10, 20mg/L |
에탄올 |
커큐민(디페룰로일메탄) |
HCT116 구형체 형성 억제 |
뉴멕시코 |
[ 49 ] |
|
엘루테로코쿠스 센티코수스 |
뿌리 |
에이치티씨티116 |
12.5, 25, 50, 100 |
메탄올 |
엘루테로사이드, 트리테르페노이드 사포닌, 글리칸 |
뉴멕시코 |
자연살해세포 활성화 및 면역기능 향상 |
[ 50 ] |
|
타버나에몬타나 디바리카타 L. |
잎 |
HT-29, HCT15 |
10, 30, 100mg/L |
에틸아세테이트, 클로로포름, 메탄올 |
알칼로이드 |
뉴멕시코 |
초나선 DNA의 풀림을 억제 |
[ 45 ] |
|
밀링토니아 호르텐시스 |
뿌리, 꽃, 잎 |
알코(RKO) |
50, 100, 200, 400, 800mg/L |
물의 |
페닐에탄오이드글리코사이드, 스쿠알렌, 살리드로사이드, 2-페닐루티노사이드 |
세포사멸 유도 |
(i) 단편화된 DNA의 증가
(ii) 항아포토시스 단백질인 Bcl-xL 및 p-BAD의 발현 감소 |
[ 46 ] |
가루 |
알코(RKO) |
200, 400, 800μg / mL |
물의 |
수용성 화합물 |
항증식효과 |
뉴멕시코 |
[ 51 ] |
|
태국 보라색 쌀 |
씨앗 |
Caco-2, 카탈로그 번호 HTB-37 |
16.11μg / mL |
메탄올 산성화 |
시아니딘-3-글루코사이드 및 페오니딘-3-글루코사이드, 안토시아닌, 페놀 화합물 |
(i) 안토시아닌 및 페놀의 항산화 작용
(ii) 대장암세포의 증식 억제 작용 |
뉴멕시코 |
[ 52 ] |
|
아노나 무리카타 |
잎 |
HCT116, HT-29 |
11.43 ± 1.87μg / ml 및 8.98 ± 1.24μg / ml |
에탄올 |
알칼로이드, 아세토게닌, 에센셜 오일 |
HT-29 및 HCT116 세포의 이동 및 침입 차단 |
(i) G1기에서 세포주기 정지
(ii) MMP, cytochrome c 누출 및 활성화 방해 |
[ 53 ] |
뉴멕시코 |
HT-29, HCT116 |
<4, <20μg / mL |
에틸아세테이트 |
안노펜토신 A, 안노펜토신 B, 안노펜토신 C, cis 및 trans-안노무리신-D-ones, 안노무리신 E |
뉴멕시코 |
암세포에서 ATP 생성 및 NADH 산화효소 억제 |
[ 54 ] |
|
피스타시아 렌티스쿠스 L. var. 치아 |
잎 |
에이치티씨티116 |
뉴멕시코 |
에탄올 |
수지, 키오스 마스틱 검(CMG)으로 알려짐 |
세포소기관에서 세포사멸의 전형적인 여러 형태학적 변화를 유발합니다. |
(i) G1 단계에서 세포주기 정지 유도
(ii) 프로카스파제 8, 9, 3 활성화 |
[ 55 ] |
수지 |
에이치티씨티116 |
100μg / mL |
헥산 |
카리오필렌 |
인간 대장암 HCT116 세포에서 아노이키스 형태의 세포사멸 유도 |
(i) G1 단계 정지 유도
(ii) 기질에 대한 접착력 상실 |
[ 56 ] |
|
미국산 인삼(Panax quinquefolius) |
생물학적 성분 |
에이치티씨티116 |
0-2.0mg/mL |
물의 |
인삼(GE) 또는 그 진세노사이드(GF) 및 폴리사카라이드(PS) |
야생형 및 p21 세포에서 GE, GF 및 PS에 의해 증식이 억제되었습니다. |
(i) 세포는 G0/G1 단계에서 정지하고 p53 및 p21 단백질이 증가합니다.
(ii) Bax 및 카스파제 3 단백질 발현이 증가합니다. |
[ 57 ] |
|
보라색 살의 감자 |
과일 |
대장암 줄기세포 |
5.0μg / mL |
에탄올, 메탄올, 에틸아세테이트 |
안토시아닌, β- 카테닌, 시토크롬 c |
CSC 증식 및 하위 단백질(c-Myc 및 사이클린 D1)의 중요한 조절자이며 Bax 및 시토크롬 c를 증가시킵니다. |
(i) p53 상태와 관계없이 시토크롬 c 수준이 상승했습니다.
(ii) 미토콘드리아 매개 세포사멸 경로
(iii) 세포질 및 핵 β- 카테닌 수준이 억제되었습니다. |
[ 58 ] |
|
파세올루스 벌가리스 |
잎 |
HT-29 |
뉴멕시코 |
에탄올 |
다당류, 올리고당류 |
세포주기 정지와 관련되거나 연관된 유전자의 변화 |
(i) 망막모세포종 인산단백질의 비활성화
(ii) G1 정지 유도
(iii) NF-jB1 억제
(iv) EGR1 발현 증가 |
[ 59 ] |
|
오푼티아속 |
과일 |
HT-29 |
5.8 ± 1.0, 7.5 ± 2.0, 12 ± 1% ( V / V ) |
하이드로알코올성 |
베타시아닌, 플라보노이드(이소람네틴 유도체) 및 페놀산(페룰산) |
뉴멕시코 |
다양한 체크포인트(G1, G2/M 및 S)에서 유도된 세포주기 정지 |
[ 60 ] |
|
노란 돼지 |
뉴멕시코 |
에이치티씨티15 |
400μg / mL |
메탄올 |
프로토카테츄산, 계피산, α- 토코페롤, β- 토코페롤, 만니톨, 트레할로스, 다중불포화지방산, 단일불포화지방산, 포화지방산 |
(i) DNA 손상을 시사하는 세포 내 p-H2A.X 수준의 증가 |
(i) G1기 세포증식 억제
(ii) 세포 내 p-H2A.X 수준 증가 |
[ 61 ] |
|
폰시루스 트리폴리아타 |
잎 |
HT-29 |
0.63μM (마이크로 미터) |
수용액(아세톤) |
β- 시토스테롤, 2-하이드록시-1,2,3-프로판트리카르복실산 2-메틸에스테르 |
β- 시토스테롤을 투여하면 세포 성장이 정지되는 것으로 관찰되었습니다. |
뉴멕시코 |
[ 62 ] |
|
Rosmarinus officinalis L. |
잎 |
SW 620, DLD-1 |
0~ 120μg /mL |
메탄올 |
폴리페놀 |
5-FU의 항증식 효과 |
5-FU 저항과 관련된 효소인 TYMS 및 TK1의 다운레귤레이션 |
[ 63 ] |
잎 |
HT-29 |
SC-RE 30μg / mL 및 CA 12.5μg / mL |
에탄올 |
폴리페놀(카르노스산(CA)과 카르노솔) |
(i) SC-RE 처리 세포에서 관찰된 콜레스테롤 축적에 주요 기여자인 VLDLR 유전자의 상향 조절
(ii) G1-S에 관련된 여러 유전자의 하향 조절 |
Nrf2 전사인자 및 UPR(Unfolded Protein Response)과 관련된 XBP1(Xbp1) 유전자와 같은 공통 조절인자의 활성화 |
[ 64 ] |
뉴멕시코 |
HT-29 |
10, 20, 30, 40, 50, 60, 70 μg/mL |
NM |
Carnosic acid, carnosol, rosmarinic acid, rosmanol |
NM |
NM |
[65] |
Leaf |
HGUE-C-1, HT-29, and SW480 |
20–40 mg/mL |
CO2-supercritical fluid extract |
Carnosic acid, carnosol, and betulinic acid |
NM |
(i) Prooxidative capability by increasing the intracellular generation of ROS
(ii) Activation of Nrf2 |
[66] |
|
Glehnia littoralis |
Leaf |
HT-29 |
50 mg/mL |
Methanolic |
Bergapten, isoimpinellin, xanthotoxin, imperatorin, panaxydiol, falcarindiol, falcarinol |
Induced apoptosis by the decreased expression of the antiapoptotic Bcl-2 mRNA |
(i) Reduced expression of Bcl-2
(ii) Reduced expression levels of iNOS and COX-2 |
[67] |
|
Verbena officinalis |
Leaf |
HCT116 |
20 mg/mL |
Aqueous |
Phenylethanoid glycosides, diacetyl-O-isoverbascoside, diacetyl-O-betonyoside A, and diacetyl-O-betonyoside A |
(i) Substantial tumor cell growth inhibitory activity
(ii) Time-dependent cytotoxicity against both cell lines |
(i) Increased lipophilicity of molecules seemed to be responsible for enhanced cytotoxicity
(ii) Antiproliferative activity is determined by the number of acetyl groups and also by their position in the aliphatic rings |
[68] |
|
Mentha spicata |
Leaf |
RCM-1 |
12.5 μg/mL |
N-Hexane |
Acetic acid 3-methylthio propyl ester (AMTP), methyl thio propionic acid ethyl ester (MTPE) |
Exhibited antimutagenic activity |
Auraptene (7-geranyloxycoumarin) having a monoterpene moiety and β-cryptoxanthin (one of the tetraterpenes) increased antibody production |
[69] |
|
Euphoria longana Lam. |
Seed |
SW 480 |
0–100 μg/mL |
Ethanolic |
Corilagin, gallic acid, ellagic acid |
(i) Antiangiogenetic properties
(ii) All fractions showed the anti-VEGF secretion activity |
Release and expression of VEGF indicated that all fractions showed the anti-VEGF secretion activity |
[70] |
|
Sutherlandia frutescens |
Flower |
Caco-2 |
1/50 dilution of the ethanolic extract |
Ethanolic |
Amino acids, including L-arginine and L-canavanine, pinitol, flavonoids, and triterpenoid saponins as well as hexadecanoic acid and γ-sitosterol |
Disruption of the key molecules in the PI3K pathway thereby inducing apoptosis |
Decrease in cell viability and increment in pyknosis as well as loss in cellular membrane integrity |
[71] |
|
Melissa officinalis |
Leaf |
HT-29, T84 |
346, 120 μg/mL |
Ethanolic |
Phenolic acids (rosmarinic acid, coumaric acid, caffeic acid, protocatechuic acid, ferulic acid, chlorogenic acid), flavonoids, sesquiterpenes, monoterpenes, triterpenes |
(i) Inhibited proliferation of colon carcinoma cells
(ii) Induced apoptosis through formation of ROS |
(i) G2/M cell cycle arrest
(ii) Cleavage of caspases 3 and 7
(iii) Induced phosphatidylserine externalization in colon carcinoma cells
(iv) Induced formation of ROS in colon carcinoma cells |
[72] |
|
Sargassum cristaefolium |
Leaf |
HT-29 |
500 mg/mL |
Ethanolic |
Fucoidans |
(i) Reduction of free radicals
(ii) DPPH radical scavenging |
Accumulation of cells in G0/G1 phase |
[73] |
|
Hedyotis diffusa |
NM |
HT-29 |
400 mg/mL |
Ethanolic and then DMSO |
Octadecyl (E)-p-coumarate, P-E-methoxy-cinnamic acid, ferulic acid, scopoletin, succinic acid, aurantiamide acetate, rubiadin |
Suppress tumor cell growth and induce the apoptosis of human CRC cells |
(i) Block G1/S progression
(ii) Induce the activation of caspases 9 and 3
(iii) Inhibit IL-6-mediated STAT3 activation
(iv) Downregulate the mRNA and protein expression levels of cyclin D1, CDK4, Bcl-1, and Bax |
[74] |
|
Zingiber officinale Roscoe |
Peel |
LoVo |
100 mg/mL |
Ethanolic |
Linoleic acid methyl ester, α-zingiberene, and zingiberone |
Interesting antiproliferative activity against colorectal carcinoma |
NM |
[75] |
|
Scutellaria barbata |
Leaf |
LoVo |
413.3 mg/L |
Methanolic |
Scutellarein, scutellarin, carthamidin, isocarthamidin, wogonin |
Induce cell death in the human colon cancer cell line |
Increase in the sub-G1 phase and inhibition of cell growth |
[76] |
|
Pistacia atlantica, Pistacia lentiscus |
Resin |
HCT116 |
100 μg/mL |
Hexane extract |
Caryophyllene |
Induce the anoikis form of apoptosis in human colon cancer HCT116 cells |
(i) Induce G1 phase arrest
(ii) Loss of adhesion to the substrate |
[56] |
|
Citrus reticulata |
Peel |
SNU-C4 |
100 μg/mL |
Methanolic |
Limonene, geranial, neral, geranyl acetate, geraniol, β-caryophyllene, nerol, neryl acetate |
Induce the apoptosis on SNU-C4, human colon cancer cells |
Expression of proapoptotic gene, Bax, and major apoptotic gene, caspase 3 |
[77] |
|
Echinacea pallida, Echinacea angustifolia, Echinacea purpurea |
Root |
COLO320 |
150 mg/mL |
Hexanic |
Caffeic acid derivatives, alkylamides, polyacetylenes, polysaccharides |
Induce apoptosis and promote nuclear DNA fragmentation |
(i) Induce apoptosis by increasing caspase 3/7 activity
(ii) Promote nuclear DNA fragmentation |
[78] |
|
Nasturtium officinale |
Leaf |
HT-29 |
50 μL/mL |
Methanolic |
Phenethyl isothiocyanate, 7-methylsulfinylheptyl, 8-methylsulfinyl |
(i) Inhibition of initiation, proliferation, and metastasis |
(i) Inhibited DNA damage
(ii) Accumulation of cells in S phase of the cell cycle |
[79] |
|
Polysiphonia |
NM |
SW480, HCT15, HCT116, DLD-1 |
20 and 40 μg/mL |
Methanolic |
2,5-Dibromo-3,4-dihydroxybenzyl n-propyl ether |
Potentially could be used as a chemopreventive agent against colon cancer |
(i) Inhibited Wnt/β-catenin pathway
(ii) Repressed CRT in colon cancer cells
(iii) Downregulated cyclin D1
(iv) Activated the NFκB pathway |
[80] |
|
Aristolochia debilis Sieb. et Zucc. |
Stem |
HT-29 |
200 μg/mL |
Methanolic |
Aristolochic acid, nitrophenanthrene carboxylic acids |
Inhibition of proliferation and induction of apoptosis in HT-29 cells |
(i) Induction of sub-G1 cell cycle
(ii) Generation of ROS and decrease of the MMP
(iii) Bax overexpression and increase of Bax/Bcl-2 ratio |
[81] |
|
Myrtaceae |
Leaf |
HCT116 |
100 μg/mL (in vitro), 200 and 100 μg/disc (in vivo) |
Methanolic |
Phenols, flavonoid, betulinic acid |
Strong inhibition of microvessel outgrowth |
(i) Inhibition of tube formation on Matrigel matrix
(ii) Inhibition of HUVECS migration (in vitro)
(iii) Decreased nutrient and oxygen supply |
[82] |
|
Spica prunellae |
Leaf |
HT-29 |
200 mg/mL (in vitro), 600 mg/mL (in vivo) |
Ethanolic |
Rosmarinic acid |
Inhibits CRC cell growth |
(i) Suppresses STAT3 phosphorylation
(ii) Regulates the expression of Bcl-2, Bax, cyclin D1, CDK4, VEGF-A, and VEGFR-2 |
[83] |
|
Phytolacca americana |
Root |
HCT116 |
3200 μg/mL |
Ethanolic |
Jaligonic acids, kaempferol, quercetin, quercetin 3-glucoside, isoquercitrin, ferulic acid |
Control of growth and spread of cancer cells |
Reduction in the expressions of MYC, PLAU, and TEK |
[84] |
|
Morus alba |
Leaf |
HCT15 |
13.8 μg/mL |
Methanolic |
Epicatechin, myricetin, quercetin hydrate, luteolin, kaempferol, ascorbic acid, gallic acid, pelargonidine, p-coumaric acid |
Cytotoxic effect on human colon cancer cells (HCT15) |
(i) Apoptosis induction also involved in the downregulation of iNOS
(ii) Fragmentation of DNA
(iii) Upregulation of caspase 3 activity |
[85] |
|
Rhodiola imbricata |
Leaf |
HT-29 |
200 μg/mL |
Acetone and methanolic |
Phenols, tannins, and flavonoids |
(i) Antioxidant activity
(ii) Inhibited proliferation of HT-29 cells |
(i) Scavenge free radicals
(ii) DPPH radical scavenging activity
(iii) Increased metal chelating activity |
[86] |
|
Asiasarum heterotropoides F. |
Dried A. radix |
HCT116 |
20 mg/mL |
Ethanolic |
Asarinin and xanthoxylol |
Inhibition of the growth of HCT116 cells |
(i) Caspase-dependent apoptosis
(ii) Regulation of p53 expression at transcription level |
[87] |
|
Podocarpus elatus |
Fruit |
HT-29 |
500 mg/mL |
Methanolic |
Phenolic and anthocyanin |
Reduction of proliferation of colon cancer cells |
(i) Cell cycle delay in S phase
(ii) 93% downregulation of telomerase activity and decrease in telomere length
(iii) Induced morphological alterations to HT-29 cells |
[88] |
|
Echinacea purpurea |
Flower |
Caco-2, HCT116 |
0–2,000 mg/mL |
Hydroethanolic |
Cichoric acid |
(i) Inhibition of proliferation
(ii) Decreased telomerase activity in HCT116 cells |
(i) Decreased telomerase activity
(ii) Activation of caspase 9
(iii) Cleavage of PARP
(iv) Downregulation of β-catenin |
[89] |
Root |
COLO320 |
150 mg/mL |
Hexanic |
Caffeic acid derivatives, alkylamides, polyacetylenes, polysaccharides |
Induce apoptosis by increasing significantly caspase 3/7 activity and promote nuclear DNA fragmentation |
(i) Increase significantly caspase 3/7 activity
(ii) Promote nuclear DNA fragmentation |
[78] |
|
Hop (Humulus lupulus L.), Franseria artemisioides |
Leaf |
NM |
100 mg/kg b.w./day |
Aqueous |
Coumarin, lignans, quinones |
30% reduction of tumor-induced neovascularization |
NM |
[90] |
NM |
Caco-2 |
NM |
Ethanolic |
Phenolic compounds, flavonoid, diterpenes |
Digestive, gastroprotective, antiseptic, anti-inflammatory, and antiproliferative activity |
NM |
[91] |
Fruit |
NL-17 |
0, 50, 100, 150 μg/mL |
Methanolic |
α-Mangostin (xanthone) |
NM |
(i) Induction of caspase 3 and caspase 9 activation
(ii) Induced cell cycle arrest at G1/G0 phase |
[92] |
Stem, bark |
HT-29 |
50 μg/mL |
Chloroform-soluble |
β-Mangostin, garcinone D, cratoxyxanthone |
Cytotoxic activity against HT-29 human colon cancer |
Inhibition of p50 and p65 activation |
[93] |
|
Annona squamosa Linn |
Leaf |
HCT116 |
8.98 μg/mL |
Crude, Aq ethyl acetate |
Acetogenins (annoreticuin & isoannoreticuin) and alkaloids dopamine, salsolinol, and coclaurine |
Inhibition of growth and proliferation of tumor cells |
(i) Reactive oxygen species (ROS) formation, lactate dehydrogenase (LDH) release
(ii) Activation of caspases 3/7, 8, and 9 |
[94] |
|
Derris scandens |
Stem |
HT-29 |
5-15 μg/mL |
Ethanolic |
Benzyls and isoflavones (genistein, coumarins, scandinone) |
Apoptosis and mitotic catastrophe of human colon cancer HT-29 cells |
(i) Inhibition of α-glucosidase activity
(ii) Scavenge free radicals |
[95] |
|
Eupatorium cannabinum |
Aerial parts |
HT-29 |
25 μg/mL |
Ethanolic |
Pyrrolizidine alkaloids (senecionine, senkirkine, monocrotaline, echimidine) |
Induced alteration of colony morphology |
(i) Upregulation of p21 and downregulation of NCL, FOS, and AURKA
(ii) Mitotic disruption and nonapoptotic cell death via upregulation of Bcl-xL, limited TUNEL labeling, and nuclear size increase |
[96] |
|
Sorghum bicolor |
The dermal layer of stalk |
HCT116 & colon cancer stem cells |
>16 and 103 μg/mL |
Phenolic-rich ethanolic, acetone |
Apigeninidin & luteolinidin |
Antiproliferative |
Target p53-dependent and p53-independent pathways |
[97] |
Dermal and seed head |
CCSC |
NM |
Methanolic |
Apigeninidin, luteolinidin, malvidin 3-O-glucoside, apigenin, luteolin, naringenin, naringenin 7-O-glucoside, eriodictyol 5-glucoside, taxifolin, catechins |
NM |
(i) Elevation of caspase 3/7 activity
(ii) Decrease in β-catenin, cyclin D1, c-Myc, and survivin protein levels
(iii) Suppression of Wnt/β-catenin signaling in a p53-dependent (dermal layer) and partial p53-dependent (seed head) manner |
[98] |
|
Hibiscus cannabinus |
Seed |
HCT116 |
KSE (15.625 μg/mL to 1,000 μg/mL) |
Ethanolic |
Gallic acid, p-hydroxybenzoic acid, caffeic acid, vanillic acid, syringic acid, and p-coumaric and ferulic acids |
Cytotoxic activity against human colon cancer HCT116 cells |
Apoptosis via blockade of mid G1-late G1-S transition thereby causing G1 phase cell cycle arrest |
[99] |
|
Salix aegyptiaca L. |
Bark |
HCT116 & HT-29 |
300 μg/mL |
Ethanolic |
Catechin, salicin, catechol and smaller amounts of gallic acid, epigallocatechin gallate (EGCG), quercetin, coumaric acid, rutin, syringic acid, and vanillin |
Anticarcinogenic effects in colon cancer cells |
Apoptosis via inhibition of phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinase signaling pathways |
[100] |
|
Rubus coreanum |
Fruit |
HT-29 |
400 μg/mL |
Aqueous |
Polyphenols, gallic acid, sanguine |
Induction of apoptosis |
(i) Induced activity of caspases 3, 7, and 9
(ii) Cleavage of poly(adenosine diphosphate-ribose) polymerase |
[101] |
|
Codonopsis lanceolata |
Root |
HT-29 |
200 μg/mL |
N-Butanol fraction |
Tannins, saponins, polyphenolics, alkaloids |
Apoptosis in human colon tumor HT-29 cells |
(i) Induced G0/G1 arrest
(ii) Enhancement of expression of caspase 3 and p53 and of the Bax/Bcl-2 ratio |
[102] |
|
Gleditsia sinensis |
Thorn |
HCT116 |
800 μg/mL |
Aqueous |
Flavonoid, lupine acid, ellagic acid glycosides |
(i) Increase in p53 levels
(ii) Downregulation of the checkpoint proteins, cyclin B1, Cdc2, and Cdc25c |
Inhibition of proliferation of colon cancer cells |
[90] |
Thorn |
HCT116 |
600 μg/mL |
Ethanolic |
NM |
Inhibitory effect on proliferation of human colon cancer HCT116 cells |
(i) Caused cell cycle arrest at G2/M phase together with a decrease of cyclin B1 and Cdc2
(ii) Progression from G2/M phase |
[91] |
|
Ligustrum lucidum |
Fruit |
DLD-1 |
50 μg/mL |
Aqueous |
Oleanolic acid, ursolic acid |
Inhibited proliferation |
(i) Reduction of Tbx3 rescued the dysregulated P14ARF-P53 signaling |
[94] |
|
Zingiber officinale |
Rhizome |
HCT116 |
5 μM |
Ethanolic |
6-Paradol, 6- and 10-dehydrogingerdione, 6- and 10-gingerdione, 4-, 6-, 8-, and 10-gingerdiol, 6-methylgingerdiol, zingerone, 6-hydroxyshogaol, 6-, 8-, 10-dehydroshogaol, diarylheptanoids |
Inhibitory effects on the proliferation of human colon cancer cells |
(i) Arrest at G0/G1 phase
(ii) Reduced DNA synthesis |
[103] |
|
Grifola frondosa |
Fruit |
HT-29 |
10 ng/mL |
Aqueous |
Phenolic compounds (pyrogallol, caffeic acid, myricetin, protocatechuic acid) |
Inhibition of TNBS-induced rat colitis |
Induced cell cycle progression in G0/G1 phase |
[104] |
|
Cucumaria frondosa |
The enzymatically hydrolyzed epithelium of the edible |
HCT116 |
<150 μg/mL |
Hydroalcoholic |
Monosulphated triterpenoid glycoside frondoside A, the disulphated glycoside frondoside B, the trisulphated glycoside frondoside C |
Inhibition of human colon cancer cell growth |
(i) Inhibition at S and G2-M phases with a decrease in Cdc25c and increase in p21WAF1/CIP
(ii) Apoptosis associated with H2AX phosphorylation and caspase 2 |
[105] |
|
Rolandra fruticosa |
Leaf & twigs |
HT-29 |
10 and 5 mg/kg/day |
Methanolic |
Sesquiterpene lactone (13-acetoxyrolandrolide) |
Antiproliferative effect against human colon cancer cells |
Inhibition of the NFκB pathway, NFκB subunit p65 (RelA), upstream mediators IKKβ and oncogenic K-ras |
[106] |
|
Cydonia oblonga Miller |
Leaf & Fruit |
Caco-2 |
250–500 μg/mL |
Methanolic |
Phenolic compound (flavonol and flavone heterosides, 5-O-caffeoylquinic acid) |
Antiproliferative effect against human kidney and colon cancer cells |
(i) Suppression of factor activation, nuclear factor-kB (NFκB) activation, protein-1 (AP-1) transcription factor, mitogen protein kinases (MAPKs), protein kinases (PKs), namely, PKC, growth-factor receptor- (GFR-) mediated pathways and angiogenesis
(ii) Cell cycle arrest and induction of apoptosis, antioxidant, and anti-inflammatory effects |
[107] |
|
Morchella esculenta |
Fruits |
HT-29 |
820 mg/mL |
Methylene chloride |
Steroids (mainly ergosterol derivatives) & polysaccharides & galactomannan |
Antioxidant activity in HT-29 colon cancer cells |
Inhibition of NF-B activation in the NF-B assay |
[108] |
|
Sedum kamtschaticum |
Aerial part |
HT-29 |
0–0.5 mg/mL |
Methanolic |
Buddlejasaponin IV |
Induced apoptosis in HT-29 human colon cancer cells |
Induction of apoptosis via mitochondrial pathway by downregulation of Bcl-2 protein levels, caspase 3 activation, and subsequent PARP cleavage |
[109] |
|
Ginseng and Glycyrrhiza glabra |
Leaf |
HT-29 |
500 μL |
Aqueous |
Uracil, adenine, adenosine, Li-glycyrrhetinic acid, quiritin |
NM |
Antiproliferative effect determination of the protein levels of p21, cyclin D1, PCNA, and cdk-2, which are the key regulators for cell cycle progression |
[110] |
|
Orostachys japonicus |
Leaf & stem |
HT-29 |
2 mg/mL |
Aqueous |
Flavonoids, triterpenoids, 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid, polysaccharide |
Antiproliferation in HT-29 colon cancer cells |
Inhibited proliferation at G2 point of the cell cycle and apoptosis via tumor suppressor protein p53 |
[111] |
|
Ginkgo biloba |
Fruit & leaf |
HT-29 |
20–320mg/L |
Aqueous |
Terpene lactones and flavonoid glycosides |
(i) Inhibited progression of human colon cancer cells
(ii) Induced HT-29 cell apoptosis |
Increase in caspase 3 activities and elevation in p53 MRN reduction in Bcl-2 mRNA |
[112] |
|
Oryza sativa |
Seed |
HT-29, SW 480, HCEC |
100 μg/mL |
Ethyl acetate |
Phenolic compound (tricin, ferulic acid, caffeic acid, and methoxycinnamic acid) |
Inhibition of the human colon cancer cell growth |
(i) Induced apoptosis by enhanced activation of caspases 8 and 3
(ii) Decrease of the number of viable SW480 and HCEC cells
(iii) Reduced colony-forming ability of these cells |
[113] |
|
Cnidium officinale Makino |
Root |
HT-29 |
305.024/mL |
Ethanolic |
Osthole, auraptenol, imperatorin |
Inhibited proliferation of human colon cancer cells (HT-29) |
Inhibition of the cellular proliferation via G0/G1 phase arrest of the cell cycle and induced apoptosis |
[114] |
|
Cnidium officinale Makino |
Root |
HT-29 |
0.1-5 mg/mL |
Aqueous |
N-(3-(Aminomethyl)benzyl)acetamidine |
Inhibited the invasiveness of cytokine-treated HT-29 cells through the Matrigel-coated membrane in a concentration-dependent manner |
(i) Reduction of HT-29 cell invasion through the Matrigel
(ii) Inhibited cytokine-mediated NO production, iNOS expression, and invasiveness of HT-29 cells
(iii) Inhibited MMP-2 activity |
[115] |
|
Long pepper (PLX) |
Fruit |
HT-29 and HCT116 |
0.10 mg/mL |
Ethanolic |
Piperidine alkaloids, piperamides, piperlongumine |
(i) Induction of apoptosis, following DNA fragmentation in HT-29 colon cancer cells in a time-dependent manner
(ii) Induced caspase-independent apoptosis |
Induced whole cell ROS production |
[116] |
|
Achyranthes aspera |
Root |
COLO 205 |
50-100 and 150-200 μg/mL |
Ethanolic (EAA) and aqueous (AAA) root extracts
Aqueous |
Phenolic compounds |
(i) Enhanced growth inhibitory effects of AAA towards COLO 205 cells in contrast to EAA
(ii) Stimulatory role of AAA in the activation of cell cycle inhibitors |
(i) Triggered mitochondrial apoptosis pathway and S phase cell cycle arrest
(ii) Increased levels of caspase 9, caspase 3, and caspase 3/7 activity |
[117] |
|
Thymus vulgaris |
Leaf |
HCT116 |
0.2, 0.4, 0.6, 0.8 mg/mL |
|
Carvacrol and thymol |
Inhibited proliferation, adhesion, migration, and invasion of cancer cells |
|
[118] |
|
Dictyopteris undulata |
NM |
SW480 |
40 μg/mL |
Ethanolic |
Cyclozonarone benzoquinone |
NM |
Induced apoptosis by reducing Bcl-2 levels, upregulating Bax, and disrupting the mitochondrial membrane potential, leading to the activation of caspases 3 and 9 |
[119] |
|
Dendrobium microspermae |
NM |
HCT116 |
0.25, 0.5, 1.0 mg/mL |
Methanolic |
NM |
NM |
Upregulation of Bax and caspases 9 and 3 and downregulation of Bcl-2 expression of genes |
[120] |
|
Cannabis sativa |
Dry flower & leaf |
DLD-1 and HCT116 |
0.3–5 μM |
Methanolic |
Cannabidiol, phytocannabinoids |
Reduced cell proliferation in a CB1-sensitive |
(i) Reduced AOM-induced preneoplastic lesions and polyps
(ii) Inhibited colorectal cancer cell proliferation via CB1 and CB2 receptor activation |
[121] |
|
Phoenix dactylifera L. |
Fruit |
Caco-2 |
0.2 mg/mL |
Aqueous |
Phenolic acids (gallic, protocatechuic, hydroxybenzoic, vanillic, isovanillic, syringic, caffeic, ferulic, sinapic, p-coumaric, isoferulic), flavonoid glycosides (quercetin, luteolin, apigenin, and kaempferol), and anthocyanidins |
Increasing beneficial bacterial growth and inhibition of proliferation of colon cancer cells |
NM |
[122] |
|
Melia toosendan |
Fruit |
SW480, CT26 |
0, 10, 20, 30, 40, 50 μg/mL |
Ethanolic |
Triterpenoids, flavonoids, polysaccharide, limonoids |
NM |
(i) Inhibited cell proliferation of SW480 and CT26 by promoting apoptosis as indicated by nuclear chromatin condensation and DNA fragmentation
(ii) Induced caspase 9 activity which further activated caspase 3 and poly(ADP-ribose) polymerase cleavage, leading the tumor cells to apoptosis |
[123] |
|
Crocus sativus L. |
Flower |
HCT116 |
0.25, 0.5, 1, 2, 4 μg/mL |
Ethanolic |
Carotenoid, pigment, crocin, crocetin |
Induced DNA damage and apoptosis |
(i) Induction of a p53 pattern-dependent caspase 3 activation with a full G2/M stop
(ii) Induced remarkable delay in S/G2 phase transit with entry into mitosis |
[124] |
Tepals and leaf |
Caco-2 |
0.42 mg/mL |
NM |
Polyphenols, glycosides of kaempferol, luteolin, and quercetin |
Proliferation of Caco-2 cells was greatly inhibited |
NM |
[125] |
|
Luffa echinata |
Fruit |
HT-29 |
50, 100, and 200 μg/mL |
Methanolic |
Amariin, echinatin, saponins, hentriacontane, gypsogenin, cucurbitacin B, datiscacin, 2-O-β-D-glucopyranosyl cucurbitacin B, and 2-O-β-D-glucopyranosyl cucurbitacin S |
Increase in the population of apoptotic cells |
(i) Inhibited the cellular proliferation of HT-29 cells via G2/M phase arrest of the cell cycle
(ii) Induced apoptotic cell death via ROS generation
(iii) Accumulation of caspase 3 transcripts of HT-29 cells |
[126] |
|
Vitis aestivalis hybrid |
Fruits (wine) |
CCD-18Co |
25, 50, 100 μg/mL |
NM |
Polyphenolics |
NM |
(i) Decreased mRNA expression of lipopolysaccharide- (LPS-) induced inflammatory mediators NFκB, ICAM-1, VCAM-1, and PECAM-1
(ii) Enhanced expression of miR-126
(iii) Decreased gene expression and reduced activation of the NFκB transcription factor, NFκB-dependent
(iv) Decrease in ROS 113MAH |
[127] |
|
Xylopia aethiopica |
Dried fruit |
HCT116 |
0, 5, 10, 15, 20, 25, 30 μg/mL |
Ethanolic |
Ent-15-oxokaur-16-en-19-oic acid (EOKA) |
NM |
(i) Induced DNA damage, cell cycle arrest in G1 phase, and apoptotic cell death |
[128] |
|
Sorghum |
Grain |
ER-β; nonmalignant young adult mouse colonocytes |
1, 5, 10, 100 μg/mL |
Aqueous |
Flavones (luteolin and apigenin), 3-deoxyanthocyanins naringenin (eriodictyol and naringenin) |
Reduced cell growth via apoptosis |
Increased caspase 3 activity |
[129] |
NM |
HT-29, HCT116 |
0.9-2.0 mg/mL |
Hydroethanolic |
Procyanidin B1, delphinidin-3-O-glucoside, tannin, cyanidin-3-O glucoside |
(i) Significantly arrested HT-29 cells in G1
(ii) Highest growth inhibition
(iii) Increased percentage of apoptotic cells |
(i) Downregulation of apoptotic proteins, such as cIAP-2, livin, survivin, and XIAP, was seen in HCT116 cells
(ii) Inhibition of tyrosine kinase |
[130] |
|
Panax notoginseng (Burk.) F.H. Chen |
Root |
LoVo and Caco-2 |
0, 100, 250, and 500 μg/mL |
Alcoholic |
Saponin, ginsenoside |
NM |
Delay in progression of the G0/G1, S, or G2/M cell cycle phases |
[131] |
|
Brassica oleracea L. var. italica |
Broccoli florets |
HCT116 |
0, 1, 2.5, 5, 10 μg/mL |
Ethanolic |
Glucoiberin, 3 hydroxy,4(α-L-rhamnopyranosyloxy), benzyl glucosinolate 4-vinyl-3-pyrazolidinone 4-(methyl sulphinyl), butyl thiourea, β-thioglucoside N-hydroxysulphates |
NM |
NM |
[132] |
|
Cistanche deserticola |
Dried stem |
SW480 |
In vivo: 0.4 g/kg/day
In vitro: 100 μg/mL |
Aqueous |
Polysaccharides, phenylethanoid glycosides |
(i) Decreased number of mucosal hyperplasia and intestinal helicobacter infection
(ii) Increased number of splenic macrophage, NK cells, and splenic macrophages |
Decreased frequency of hyperplasia and Helicobacter hepaticus infection of the intestine |
[133] |
|
Chaenomeles japonica |
Fruit |
Caco-2 and HT-29 |
10, 25, 50, 75, 100, 125, 150 μM CE |
NM |
Procyanidins |
NM |
NM |
[134] |
|
Prunus mume |
Fruit |
SW480, COLO, and WiDr |
150, 300, and 600 μg/mL |
Hydrophobic |
Triterpenoid saponins |
NM |
(i) Inhibited growth and lysed SW480, COLO, and WiDr
(ii) Induction of massive cytoplasmic vacuoles |
[135] |
|
Solanum lyratum |
NM |
COLO 205 |
50, 100, 200, 300, 400 μg/mL |
EtOH |
β-Lycotetraosyl |
Induced S phase arrest and apoptosis |
(i) Induced DNA fragments
(ii) Increased the levels of p27, p53, cyclin B1, active-caspase 3, and Bax
(iii) Decreased the levels of Cdk1, pro-caspase 9, Bcl-2 and NF-ÎB, p65, and p50 |
[136] |
|
Onopordum cynarocephalum |
Aerial parts |
HCT116, HT-29 |
0, 0.04, 0.12, 0.2, 0.4, 1.2 mg/mL
0, 0.2, 0.4, 1.2, 2.0, 3.0 mg/mL |
Aqueous |
Flavonoids, lignans, and sesquiterpene lactones |
NM |
(i) Increase in the expression of proapoptotic proteins such as p53, p21, and Bax
(ii) Inhibition of the antiapoptotic protein Bcl-2
(iii) Decrease in cyclin D1 protein |
[137] |
|
Eleutherine palmifolia |
Bulbs |
SW480 |
2.5, 5, 10 μg/mL |
MeOH |
Eleutherin, isoeleutherin |
NM |
(i) Inhibited the transcription of TCF/β-catenin
(ii) Decrease in the level of nuclear β-catenin protein |
[138] |
|
Asparagus officinalis |
Spears |
HCT116 |
76 μg/mL |
Acetone |
Steroidal saponins (HTSA-1, HTSAP-2, HTSAP-12, HTSAP-6, HTSAP-8) |
NM |
(i) Inhibition of Akt, p70S6K, and ERK phosphorylation
(ii) Induction of caspase 3 activity, PARP-1 cleavage, DNA fragmentation, G0/G1 cell cycle arrest by reducing the expression of cyclins D, A, and E |
[139] |
|
Phyllanthus emblica L. |
Seed, pulp |
HCCSCs, HCT116 |
200 μg/mL |
Methanolic |
Trigonelline, naringin, kaempferol, embinin, catechin, isorhamnetin, quercetin |
(i) Suppressed proliferation
(ii) Induced apoptosis independent from p53 stemness property (in HCCSCs)
(iii) Antiproliferative properties |
(i) Suppressed cell proliferation and expression of c-Myc and cyclin D1
(ii) Induced intrinsic mitochondrial apoptotic signaling pathway |
[140] |
|
Red grape |
NM |
HT-29, HCT116 |
0.9-2.0 mg/mL |
Hydroethanolic |
Delphinidin glycosides, quercetin derivatives, delphinidin-3-O-glucoside (high), cyanidin-3-O-glucoside |
(i) Highest growth inhibition
(ii) Increased the percentage of apoptotic cells |
(i) Downregulation of apoptotic proteins, such as cIAP-2, livin, survivin, and XIAP
(ii) Inhibition of tyrosine kinase |
[130] |
|
Black lentil |
NM |
HT-29, HCT116 |
0.9-2.0 mg/mL |
Hydroethanolic |
Delphinidin glycosides, procyanidin B1, delphinidin-3-O-glucoside (high), cyanidin-3-O-glucoside |
(i) Significantly arrested HT-29 cells in G1
(ii) Highest growth inhibition
(iii) Increased percentage of apoptotic cells |
(i) Downregulation of apoptotic proteins, such as cIAP-2, livin, survivin, and XIAP
(ii) Inhibition of tyrosine kinase |
[130] |
|
Graptopetalum paraguayense |
Leaf |
Caco-2, BV-2 |
0.2, 0.4, 0.6, 0.8, 1.0 mg/mL |
Hydroethanolic |
Oxalic acid, hydroxybutanedioic acid, gallic acid, quercetin, chlorogenic acid glucans with fucose, xylose, ribose (GW100) arabino-rhamnogalactans (GW100E) |
(i) Great potential in antiproliferation
(ii) Significant immunomodulatory activities on BV-2 cells and interleukin-6 (IL-6) (GW100) |
(i) Scavenging α, α-diphenyl-β-picrylhydrazyl radicals (DPPH) (GW100E excelled in scavenging DPPH), 2,2-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid] radicals (ABTS), superoxide anions (O2) (GW100)
(ii) Significant inhibition of tumor necrosis factor-a (TNF-a), scavenging ABTS and O2 |
[141] |
|
Butea monosperma |
Flower |
SW480 |
200, 370 μg/mL |
Floral |
n-Butanol |
Significant antiproliferative effect |
(i) Significantly downregulated the expression of Wnt signaling proteins such as β-catenin, APC, GSK-3β, cyclin D1, and c-Myc
(ii) Increased intracellular level of ROS |
[142] |
|
Rehmannia glutinosa |
NM |
CT26 |
5, 20, 80 μM |
NM |
Catalpol |
Inhibited proliferation and growth invasion of colon cancer cells |
(i) Downregulated MMP-2 and MMP-9 protein expressions
(ii) Reduction in the angiogenic markers secretions |
[143] |
|
Telectadium dongnaiense |
Bark |
HCT116 |
1.5, 2.0 μg/mL |
MeOH extract |
4-Dicaffeoylquinic acid, quercetin 3-rutinoside, periplocin |
NM |
(i) Inhibition of β-catenin/TCF transcriptional activity and effects on Wnt/β-catenin
(ii) Downregulation of the expression of Wnt target genes |
[144] |
|
Gloriosa superba |
Root |
SW620 |
30 ng/mL |
Protein hydrolysate extract |
Protein hydrolysate |
NM |
(i) Upregulation of p53
(ii) Downregulation of NFκB |
[145] |
|
Boswellia serrata |
Resin |
HT-29 |
100, 150 μg |
Methanolic |
Boswellic acid |
Decreased cell viability |
(i) Reduction in mPGES-1, VEGF, CXCR4, MMP-2, MMP-9, HIF-1, PGE2 expression
(ii) Increment in the caspase 3 activity
(iii) Inhibition of cell migration and vascular sprout formation |
[146] |
|
Typhonium flagelliforme |
Leaf |
WiDr |
70 μg/mL |
Ethyl acetate |
Glycoside flavonoid, isovitexin, alkaloids |
NM |
Inhibition of COX-2 expression |
[28] |
|
Diospyros kaki |
Fruit |
HT-29 |
2,000 μg/mL |
Hydroacetone extract |
Polyphenol |
Impaired cell proliferation and invasion |
NM |
[147] |
|
Carpobrotus edulis |
Leaf |
HCT116 |
1,000 mg/mL |
Hydroethanolic |
Gallic acid, quercetin, sinapic acid, ferulic acid, luteolin 7-o-glucoside, hyperoside, isoquercitrin, ellagic acid, isorhamnetin 3-O-rutinoside |
Inhibited proliferation |
(i) Possession of high DPPH scavenging activity and effective capacity for iron binding
(ii) Inhibition of NO radical, linoleic acid peroxidation, protein glycation, and oxidative damage |
[148] |
|
Piper methysticum |
Root |
HT-29 |
10, 20, 30, 40, 50 μg/mL |
Aqueous |
11-Hydroxy-12-methoxydihydrokavain, 11-hydroxy-12-methoxydihydrokavain, prenyl caffeate, pinostrobin chalcone, 11-methoxytetrahydroyangonin, awaine, methysticin, dihydromethysticin, 5,6,7,8-tetrahydroyangonin, kavain, 7,8-dihydrokavain, yangonin, desmethoxyyangonin, flavokawain B |
Inhibited the growth |
NM |
[26] |
|
Salvia ballotiflora |
Ground aerial parts |
CT26 |
6.76 μg/mL |
Hexane-washed chloroform extract |
19-Deoxyicetexone, 7,20-dihydroanastomosine, icetexone, 19-deoxyisoicetexone |
Cytotoxic activity |
NM |
[149] |
|
Tinospora cordifolia |
Stem |
HCT116 |
1, 10, 30, 50 μM |
Hydroalcoholic |
Clerodane furano diterpene glycoside, cordifoliosides A and Β, sitosterol, ecdysterone, 2β,3β:15,16-diepoxy-4α, 6β-dihydroxy-13(16),14-clerodadiene-17,12:18,1-diolide |
Induced chromatin condensation and fragmentation of nuclei of few cells |
(i) Considerable loss of MMP
(ii) Decreased in mitochondria function
(iii) Increased cytochrome c in the cytosol
(iv) Induced ROS/oxidative stress
(v) Increased autophagy |
[150] |
|
Euterpe oleracea |
Fruit |
NM |
35 μg/mL |
Hydroethanolic |
Vanillic acid, orientin, isoorientin |
NM |
(i) Scavenging capacity towards ROO and HOCl
(ii) Inhibition of nitroso compound formation |
[151] |
|
Salvia miltiorrhiza |
NM |
HCT116 |
7.4 ± 1.0, 4.4 ± 0.5 μg/mL |
Ethanolic |
Diterpene quinone |
NM |
Decreased levels of pro-caspases 3 and 9 |
[152] |
|
Coffea |
Bean |
HCT116 |
1 mg/mL |
Aqueous |
Chlorogenic acid complex (CGA7) |
NM |
(i) DNA fragmentation, PARP-1 cleavage, caspase 9 activation, downregulation of Bcl-2 and upregulation of Bax |
[153] |
|
Illicium verum |
Fruit |
HCT116 |
10 mg/mL |
Ethanolic |
Gallic acid quercetin |
Induction of apoptosis and inhibition of key steps of metastasis |
NM |
[154] |
|
Garcinia propinqua Craib |
Leaf |
HCT116 |
NM |
CH2Cl2 extract |
Benzophenones, xanthones, and caged xanthones |
Potent inhibitory cytotoxicities |
NM |
[155] |
Stem, bark |
HCT116 |
14.23, 23.95 μM |
MeOH, CH2Cl2, and EtOAc extract |
Xerophenone A, doitunggarcinones A and B, sampsonione, 7β-H-11-benzoyl-5α-ydroxy-6, 10-tetramethyl-1-(3-methyl-2-butenyl)-tetracyclotetradecane-2,12,14-trione, hypersampsone M, assiguxanthone A (cudraxanthone Q), 40 10-O-methylmacluraxanthone (16), 41- and 5-O-methylxanthone V1 |
NM |
NM |
[156] |
|
Malus pumila Miller cv. Annurca |
Fruit |
Caco-2 |
400 mg/L |
Methanolic |
Chlorogenic acid, (+)catechin, (–)epicatechin, isoquercetin, rutin, phloridzin, procyanidin B2, phloretin, quercetin |
WNT inhibitors and reduced WNT activity elicited by WNT5A |
NM |
[157] |
|
Malus domestica cv. Limoncella |
Fruit |
Caco-2 |
400 mg/L |
Methanolic |
Chlorogenic acid, (+)catechin, (–)epicatechin, isoquercetin, rutin, phloridzin, procyanidin B2, phloretin, quercetin |
WNT inhibitors and reduced WNT activity elicited by WNT5A |
NM |
[157] |
|
Coix lacryma-jobi var. ma-yuen |
Leaf |
HCT116 |
0.5, 1 mg/mL |
Aqueous |
Coixspirolactam A, coixspirolactam B, coixspirolactam C, coixlactam, methyl dioxindole-3-acetate |
NM |
Inhibited migration, invasion, and adhesion via repression of the ERK1/2 and Akt pathways under hypoxic conditions |
[158] |
|
Mesua ferrea |
Stem, bark |
HCT116, HT-29 |
3.3, 6.6, and 11.8 μg/mL |
NM |
Fractions (α-amyrin, SF-3, n-Hex) |
Downregulation of multiple tumor promoter |
Upregulation of p53, Myc/Max, and TGF-β signaling pathways |
[159] |
|
Taraxacum |
Root |
SGC7901, BGC823 |
3 mg/mL |
Aqueous |
NM |
NM |
Proliferation and migration through targeting lncRNA-CCAT1 |
[160] |
|
Portulaca oleracea |
Leaf |
HT-29 CSCs |
2.25 μg/mL |
Alcoholic |
Oxalic, malic acid |
NM |
Inhibited expression of the Notch1 and β-catenin genes, regulatory and target genes that mediate the Notch signal transduction pathway |
[161] |
|
Hordeum vulgare L. |
NM |
HT-29 |
NM |
Aqueous & juice |
Protein, dietary fiber, the B vitamins, niacin, vitamin B6, manganese, phosphorus, carbohydrates |
(i) Inhibited proliferation of cancer cells
(ii) Cytotoxic activity |
Free radical scavenging activity |
[162] |
|
Paraconiothyrium sp. |
NM |
COLO 205 and KM12 |
12.5 μM |
Methyl ethyl ketone extract |
n-Hexane, CH2Cl2, EtOAc, and MeOH fractions (A−D) |
(i) Growth inhibitory activity
(ii) Antiproliferative effect |
NM |
[163] |
|
Mentha×piperita |
Leaf |
HCT116 |
5, 10, 20, 30, 40, 50 μg/mL |
Aqueous |
Polyphenols |
NM |
Inhibited replication of DNA and transcription of RNA which induce the ROS |
[164] |
|
Mammea longifolia Planch. and Triana |
Fruit |
SW480 |
25, 50, 100 μg/mL |
Methanolic |
NM |
NM |
Mitochondria-related apoptosis and activation of p53 |
[165] |
|
Rollinia mucosa (Jacq.) Baill. |
NM |
HCT116, SW-480 |
<4, <20 μg/mL |
EtOH |
Rollitacin, jimenezin, membranacin, desacetyluvaricin, laherradurin |
Cytotoxic activity |
NM |
[54] |
|
Annona diversifolia Saff. |
NM |
SW-480 |
0.5 μg/mL |
NM |
Cherimolin-2 |
Cytotoxic activity |
NM |
[54] |
|
A. purpurea Moc. & Sessé ex Dunal |
NM |
HT-29 |
1.47 μg/mL |
CHCl3-MeOH |
Purpurediolin, purpurenin, annoglaucin, annonacin A |
Cytotoxic activity |
NM |
[54] |
|
Viguiera decurrens (A.Gray) A. Gray |
NM |
NM |
3.6 μg/mL |
Hex; EtOAc; MeOH |
β-Sitosterol-3-O-β-D-glucopyranoside; β-D-glucopyranosyl oleanolate; β-sitosterol-3-O-β-D-glucopyranoside, and oleanolic acid-3-O-methyl-β-D-glucuronopyranoside ronoate |
Cytotoxic activity |
NM |
[54] |
|
Helianthella quinquenervis (Hook.) A. Gray |
NM |
HT-29 |
2-10 μg/mL |
NM |
Demethylencecalin |
Cytotoxic activity |
NM |
[54] |
|
Smallanthus maculatus (Cav.) H. Rob. |
NM |
HCT15 |
<20 μg/mL |
Acetone |
Fraction F-4, fraction F-5, ursolic acid |
Cytotoxic activity |
NM |
[54] |
|
Bursera fagaroides (Kunth) Engl. |
NM |
HF6 |
1.8×10−4 to 2.80 μg/mL |
Hydroalcoholic |
Podophyllotoxin, β-peltatin-A methyl ether, 5′-desmethoxy-β-peltatin-A methyl ether, desmethoxy-yatein, deoxypodophyllotoxin, burseranin, acetyl podophyllotoxin |
NM |
(i) Inhibitor of microtubules
(ii) Ability to arrest cell cycle in metaphase |
[54] |
|
Viburnum jucundum C.V. Morton |
NM |
HCT15 |
<20 μg/mL |
Acetone |
Ursolic acid |
Cytotoxic activity |
NM |
[54] |
|
Hemiangium excelsum (Kunth) A.C.Sm. |
NM |
HCT15 |
<10 (μg/mL) |
MeOH |
PE, EtOAc, MeOH |
Cytotoxic activity |
NM |
[54] |
|
Hyptis pectinata (L.) Poit. |
NM |
Col2 |
<4, <20 μg/mL |
NM |
Pectinolide A, pectinolide B, pectinolide C, α-pyrone, boronolide, deacetylepiol-guine |
Cytotoxic activity |
NM |
[54] |
|
H. verticillata Jacq. |
NM |
Col2 |
<4,<20 μg/mL |
NM |
Dehydro-β-peltatin, methyl ether dibenzylbutyrolactone, (-)-yatein, 4′-demethyl-deoxypodophyllotoxin |
Nonspecific cytotoxic activity |
NM |
[54] |
|
H. suaveolens (L.) |
NM |
HF6 |
2.8-12 μg/mL |
Chloroform and butanol |
β-Apopicropodophyllin |
Nonspecific cytotoxic activity |
NM |
[54] |
|
Salvia leucantha Cav. |
Leaf, root, stem |
HF6, HT-29, HCT15 |
14.9, 12.7, 9.9 μg/mL |
CHCl3 |
NM |
Cytotoxic activity |
NM |
[54] |
|
Vitex trifolia L. |
NM |
HCT15 |
3.5 to <1 (μg/mL) |
Hexane and dichloromethane |
Salvileucalin B, Hex: leaf, Hex: stem, DCM: leaf, DCM: stem |
Cytotoxic activity |
NM |
[54] |
|
Persea americana Mill. |
NM |
HT-29 |
<4 μg/mL and <20 μg/mL |
Ethanolic |
1,2,4-trihydroxynonadecan, 1,2,4-trihydroxyheptadec-16-ene, 1,2,4-trihydroxyheptadec-16-yne |
Cytotoxic activity |
NM |
[54] |
|
Linum scabrellum |
Roots, aerial parts |
HF6 |
0.2, 0.5, 2.3 μg/mL |
Chloroform and butanol |
DCM: MeOH, 6MPTOXPTOX |
NM |
(i) Induction of cell cycle arrest in G2/M
(ii) Inhibition of tubulin polymerization |
[54] |
|
Phoradendron reichenbachianum (Seem.) Oliv. |
NM |
HCT15 |
3.6, 3.9, and 4.3 μg/mL |
NM |
Moronic acid |
Cytotoxic activity |
NM |
[54] |
|
Cuphea aequipetala Cav. |
NM |
HCT15 |
18.70 μg/mL |
Acetone |
NM |
Cytotoxic inactivity |
NM |
[54] |
|
Galphimia glauca Cav. |
NM |
HCT15 |
0.63, 0.50, 1.99 μg/mL |
EtOH, MeOH, aqueous |
NM |
Cytotoxic activity |
NM |
[54] |
|
Mimulus glabratus Kunth |
NM |
HF6 |
12.64 μg/mL |
MeOH |
NM |
Cytotoxic activity |
NM |
[54] |
|
Picramnia antidesma Sw. |
NM |
HCT15 |
0.6 to 4.5 μM |
NM |
10-Epi-uveoside, uveoside, picramnioside E, picramnioside D |
Cytotoxic activity |
NM |
[54] |
|
Penstemon barbatus (Cav.) Roth |
NM |
HF6 |
15.19 μg/mL |
MeOH |
NM |
Cytotoxic activity |
NM |
[54] |
|
P. campanulatus (Cav.) Willd. |
NM |
HF6 |
6.74 μg/mL |
MeOH |
NM |
Cytotoxic activity |
NM |
[54] |
|
Veronica americana Schwein. ex Benth. |
NM |
HF6 |
0.169 and 1.46 μg/mL |
MeOH |
NM |
Cytotoxic activity |
NM |
[54] |
|
Zea mays L. |
NM |
HCT116, SW-480, SW-620 |
NM |
NM |
13-Hydroxy-10-oxo-trans-11-octadecenoic acid |
Cytotoxic activity |
NM |
[54] |
|
Colubrina macrocarpa (Cav.) G. Don |
NM |
HCT15 |
10, 2.1, 9.1 μg/mL |
PE, EtOAc, MeOH |
NM |
Cytotoxic activity |
NM |
[54] |
|
Coix lacryma-jobi |
Seed, endosperm, and hull |
HT-29 |
0.1–1,000 μg/mL |
Methanolic, hexane |
Phytosterols (campesterol, stigmasterol, and β-sitosterol), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoicacid (EPA) and docosahexaenoic acid (DHA), linoleic acid |
NM |
(i) Influence of signal transduction pathways that involve the membrane phospholipids
(ii) Enhancement of ROS generation and decrease of cell antioxidant capacity |
[166] |
|
Abutilon indicum |
Leaf |
HT-29 |
210 μg/mL |
Aqueous |
Flavonoids (4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, 2-ethoxy-4-vinylphenol, N,N′-dimethylglycine, lup-20(29)-en-3-one, linolenin, 1-mono-, 9-hexadecanoic acid methyl ester, linolenic acid methyl ester), phenolic (amino acids, terpenoids, fatty acids, methyl palmitoleate) |
NM |
(i) Increase in the levels of reactive oxygen species and simultaneous reduction in cellular antioxidant, mitochondrial membrane loss, DNA damage, and G1/S phase cell cycle arrest |
[167] |
|
Galla rhois |
NM |
HCT116, HT-29 |
12.5, 25, 50, 100, 200 μg/mL |
Aqueous with steaming process |
Gallotannins |
Increased contents of gallic acid and ellagic acid |
(i) Induced apoptosis through the activation of caspases 3, 8, 9
(ii) Modulated activation of mitogen and protein kinases, p38, and c-Jun NH2-terminal kinase |
[168] |
|
Artemisia annua Linné |
Powder |
HCT116 |
20, 30, 40, 60, 80, 100 μg/mL |
Ethanolic |
Phenolic compounds |
Inhibited cell viability and increased LDH release |
(i) PTEN/p53/PDK1/Akt signal pathways through PTEN/p53 induce apoptosis
(ii) Increased apoptotic bodies, caspase 3 and 7 activation
(iii) Regulated cytochrome c translocation to the cytoplasm and Bax translocation to the mitochondrial membrane |
[169] |
|
Nelumbo nucifera stamen |
Powder |
HCT116 |
100, 200, 400 μg/mL |
Ethanolic crude |
NM |
NM |
(i) Increased the sub-G1 population, mRNA levels of caspases 3 and 8, levels of IκBα and caspase 9
(ii) Modulated the Bcl-2 family mRNA expression
(iii) Reduced the mRNA levels of NFκB |
[170] |
|
Corn silk |
NM |
LoVo, HCT116 |
1.25, 2.5, 5, 10, 20 μg/mL |
Aqueous |
Proteins, polysaccharides, flavonoid, vitamins, tannins, alkaloids, mineral salts, steroids |
NM |
(i) Increase in the Bax, cytochrome c, caspases 3 and 9 levels |
[171] |
|
Lycium barbarum L. |
Powder |
HT-29 |
1, 2, 3, 4, 5 μg/mL |
NM |
Neoxanthin, all-trans-β-cryptoxanthin, polysaccharides, carotenoids, flavonoids |
NM |
(i) Upregulation of p53 and p21 expression
(ii) Downregulation of the CDK2, CDK1, cyclin A, and cyclin B expression
(iii) Arrest in the G2/M phase of cell cycle |
[172] |
|
Chrysobalanus icaco L. |
Freeze-dried fruit |
HT-29 |
1, 2.5, 5, 10, 20 μg/mL |
Crude ethyl acetate |
Delphinidin, cyanidin, petunidin, and peonidin |
NM |
(i) Increased intracellular ROS production
(ii) Decreased TNF-α, IL-1β, IL-6, and NFκB1 expressions |
[173] |
|
Zanthoxylum piperitum De Candolle |
Fruit |
Caco-2, DLD-1 |
200 μg/mL |
Aqueous |
NM |
NM |
(i) Increased the phosphorylation of c-Jun N-terminal kinase (JNK) |
[174] |
|
Celtis aetnensis (Tornab.) Strobl (Ulmaceae) |
Twigs |
Caco-2 |
5, 50, 100, 250, or 500 μg/mL |
Methanolic |
Flavonoid and triterpenic compounds |
NM |
(i) Increase in the levels of ROS
(ii) Decrease in RSH levels and expression of HO-1 |
[175] |
|
Rosa canina |
Peel and pulp |
Caco-2 |
62.5, 125, 250, 500 μg/mL |
Total extract (fraction 1), vitamin C (fraction 2), neutral polyphenols (fraction 3), and acidic polyphenols (fraction 4) |
Polyphenols |
Decreased production of reactive oxygen species (ROS) |
NM |
[176] |
|
Rhazya stricta |
Leaf |
HCT116 |
47, 63, 79, and 95 μg/cm2 |
Crude alkaloid |
Alkaloids |
NM |
(i) NF κ B 및 AP-1 단백질 의 DNA 결합 및 전사 활동 하향 조절
(ii) Bax, 카스파제 3/7 및 9, p53, p21 및 Nrf-2 수준 증가
(iii) ERK MAPK, Bcl-2, 사이클린 D1, CDK-4, survivin 및 VEGF 발현 감소 |
[ 177 ] |
|
그린 커피 |
뉴멕시코 |
카코-2 |
10~ 1,000μg /mL |
뉴멕시코 |
5-카페오일퀸산(5-CQA), 3,5-디카페오일퀸산(3,5-DCQA), 페룰산(FA), 카페산(CA), 디하이드로카페산(DHCA), 디하이드로페룰산(DHFA) |
암세포의 생존력 감소 |
뉴멕시코 |
[ 178 ] |
|
플로렌시아 미크로필라 |
잎 |
HT-29 |
뉴멕시코 |
에탄올과 아세톤 |
페놀 화합물 |
뉴멕시코 |
(i) IL-8 억제
(ii) Bax/Bcl-2 비율 증가 및 TNF family 발현에 의한 세포사멸 활성화 |
[ 179 ] |