Natural products and colon cancer: current status and future prospects.

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Rajamanickam S, Agarwal R. Drug Dev Res. 2008 Nov 1;69(7):460-471.

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Carcinogenesis is a multistage process consisting of initiation, promotion and progression phases. Thus, the multistage sequence of events has many phases for prevention and intervention. Chemoprevention, a novel approach for controlling cancer, involves the use of specific natural products or synthetic chemical agents to reverse, suppress or prevent premalignancy before the development of invasive cancer. Several natural products, such as, grains, nuts, cereals, spices, fruits, vegetables, beverages, medicinal plants and herbs and their various phytochemical constituents including, phenolics, flavonoids, carotenoids, alkaloids, nitrogen containing as well as organosulfur compounds confer protective effects against wide range of cancers including colon cancer. Since diet has an important role in the etiology of colon cancer, dietary chemoprevention received attention for colon cancer prevention. However, identification of an agent with chemopreventive potential requires in vitro studies, efficacy and toxicity studies in animal models before embarking on human clinical trials. A brief introduction about colon cancer and the role of some recent natural products in colon cancer chemoprevention with respect to multiple molecular mechanisms in various in vitro, in vivo and clinical studies are described in this review.

In vitro studies showing chemopreventive potential of natural products.

Reference Natural product Cells Mechanisms of action

Seeram et al., 2006 Blackberry, black Raspberry, Blueberry, Cranberry, red Raspberry, and Strawberry HT-29 and HCT-116 Growth inhibition
Apoptosis induction

Kaur et al., 2006 Grape seed extract HT-29 and LoVo G1 phase cell cycle arrest
?Caspase 3 dependent apoptotic cell death.
?Decrease in G1 phase-associated cyclins and cyclin-dependent kinases
Park et al., 2007 Resveratrol HT-29 Apoptosis induction
Engelbrecht et al., 2007 CaCo2 ?PI3-K pathway
Zykova et al., 2008 HT-29 ?Cox-2 & PGE2

Agarwal et al., 2003 Silibinin HT-29 Cell cycle arrest; CDKIs and Apoptosis induction
Hogan et al., 2007 Silibinin Fet, Geo, and HCT116 Cell cycle arrest

Sang et al., 2006 Wheat bran and its phytosterols HCT-116 Growth inhibition
Tian and Song 2006 IP6 HT-29 ?p21 expression

Su et al., 2006 Curcumin Colo205 Activation of caspase 3
?Bax, cytochrome C, p53 and p21
?Bcl-2 and MMP-2

Sriram et al., 2008 DAS Colo 320 DM G2/M phase arrest, ?Caspase 3 activation
?ERK-2 activity, ?p21 expression
Druesne et al., 2004 DADS HT-29 and CaCo2 Apoptosis induction,?Cox-2 and iNOS
Ban et al., 2007 Thiacremonone SW620 and HCT-116 ?Invasion
Matsuura et al., 2006 Aged garlic extract SW480 and SW620

Jung et al., 2001 EGCG HT-29 ?VEGF expression
Porath et al., 2005 HT-29 and T84 ?PGE2 synthesis
Shimizu et al., 2005a HT-29 ?EGFR,?COX-2
Shimizu et al., 2005b CaCo2, HCT-116, HT-29, SW480, and SW837 ?p-HER2, -ERK and -Akt
Ju et al., 2005 HT-29 ?c-Myc and cyclin D1

Kang et al., 2008 Soybean saponin HT-29 ?Invasion

Chemopreventive effect of natural products and their active constituents against colorectal cancer in various in vivo models.

References Natural product Animal models

Sengupta et al.,2004 Garlic and tomato AOM

Taché et al., 2007 Onion AOM

Tessitore et al., 2000 Resveratrol AOM

Reddy et al., 2000 and
Jenab and Thompson, 2000
wheat bran AOM

Hakkak et al., 2001 Soy protein AOM

Bobe et al., 2008 Navy beans AOM

Lala et al., 2006 Bilberry and grape AOM

Barth et al., 2005 Cloudy apple juice DMH

Nalini et al., 2006 and Cumin, and black pepper DMH

Kamaleeswari et al, 2006 Caraway DMH

Manju and Nalini, 2005 Ginger DMH

Sengottuvelan and Nalini,2006 Resveratrol DMH

Devasena et al. 2003 and 2007 Fenugreek seeds DMH

Perkins et al., 2002 and
Mahmoud et al.,2000
Curcumin APC min mice
Li et al., 2007 Curcumin HT-29 and LoVo xenografts

Kaur et al., 2006 Grape seed extract HT-29 xenograft

Singh et al., 2008 Silibinin HT-29 xenograft

Bobe et al., 2006 Tart cherry extract APC min mice

Rajakangas et al., 2008 White currant Min mice

Issa et al., 2007 Green tea AOM-APC min mice
Roomi et al., 2005 Green tea HCT-116 xenograft
Ju et al., 2005 EGCG APC min mice
Hao et al., 2007 EGCG and polyphenon B APC min mice
Patel et al., 2008 Thearubigins DMH

Chung et al., 2000 Sulforaphane and PEITC AOM
Hu et al, 2006 Sulforaphane APC min mice
Khor et al., 2008 PEITC APC min mice

This review summarized chemopreventive efficacy of natural products and their constituent phytochemicals in various in vitro and in vivocolon cancer models. All these results strengthen the fact that natural products can modulate various molecular pathways involved in cancer initiation and progression. Studies described here and elsewhere clearly highlight the use of natural products as novel chemopreventive agents for colon cancer intervention. It is expected that future studies with natural products will define various molecular mechanisms and targets for tumor growth inhibition, apoptosis, and especially angioprevention. To date, chemoprevention clinical trials with natural products conducted in colon cancer are very limited. Extensive clinical research is warranted to evaluate further safety and chemopreventive efficacy of natural products either alone or in combination with chemotherapeutic agents against colon cancer.


Agarwal C, Singh RP, Dhanalakshmi S, Tyagi AK, Tecklenburg M, Sclafani RA, Agarwal R. Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells. Oncogene. 2003;22:8271–8282. [PubMed]
American Cancer Society. Cancer facts and figures 2007–2008. American Cancer Society; 2007–2008.
Ban JO, Yuk DY, Woo KS, Kim TM, Lee US, Jeong HS, Kim DJ, Chung YB, Hwang BY, Oh KW, Hong JT. Inhibition of cell growth and induction of apoptosis via inactivation of NF-kappaB by a sulfur compound isolated from garlic in human colon cancer cells. J Pharmacol Sci. 2007;104:374–383. [PubMed]
Barth SW, Fändrich C, Bub A, Dietrich H, Watzl B, Will F, Briviba K, Rechkemmer G. Cloudy apple juice decreases DNA damage, hyperproliferation and aberrant crypt foci development in the distal colon of DMH-initiated rats. Carcinogenesis. 2005;26:1414–1421.[PubMed]
Bermúdez-Soto MJ, Larrosa M, Garcia-Cantalejo JM, Espìn JC, Tomá-Barberan FA, Garcìa-Conesa MT. Up-regulation of tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 in human colon cancer Caco-2 cells following repetitive exposure to dietary levels of a polyphenol-rich chokeberry juice. J Nutr Biochem. 2007;18:259–271. [PubMed]
Bobe G, Barrett KG, Mentor-Marcel RA, Saffiotti U, Young MR, Colburn NH, Albert PS, Bennink MR, Lanza E. Dietary cooked navy beans and their fractions attenuate colon carcinogenesis in azoxymethane-induced ob/ob mice. Nutr Cancer. 2008;60:373–381. [PMC free article] [PubMed]
Bobe G, Wang B, Seeram NP, Nair MG, Bourquin LD. Dietary anthocyanin-rich tart cherry extract inhibits intestinal tumorigenesis in APC(Min) mice fed suboptimal levels of sulindac. J Agric Food Chem. 2006;54:9322–9328. [PubMed]
Bode AM, Dong Z. Targeting signal transduction pathways by chemopreventive agents. Mutat Res. 2004;555:33–51. [PubMed]
Cai H, Al-Fayez M, Tunstall RG, Platton S, Greaves P, Steward WP, Gescher AJ. The rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesis in ApcMin mice. Mol Cancer Ther. 2005;4:1287–1292. [PubMed]
Cappell MS. From colonic polyps to colon cancer: pathophysiology, clinical presentation, screening and colonoscopic therapy. Minerva Gastroenterol Dietol. 2007;53:351–373. [PubMed]
Chen A, Xu J, Johnson AC. Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene. 2006;25:278–287. [PubMed]
Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21:2895–2900. [PubMed]
Chung FL, Conaway CC, Rao CV, Reddy BS. Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis. 2000;21:2287–2291. [PubMed]
Collett GP, Campbell FC. Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells. Carcinogenesis. 2004;25:2183–2189. [PubMed]
Devasena T, Venugopal Menon P. Fenugreek seeds modulate 1,2-dimethylhydrazineinduced hepatic oxidative stress during colon carcinogenesis. Ital J Biochem. 2007;56:28–34. [PubMed]
Dragnev KH, Feng Q, Ma Y, Shah SJ, Black C, Memoli V, Nugent W, Rigas JR, Kitareewan S, Freemantle S, Dmitrovsky E. Uncovering novel targets for cancer chemoprevention. Recent Results Cancer Res. 2007;174:235–243. [PubMed]
Druesne N, Pagniez A, Mayeur C, Thomas M, Cherbuy C, Duee PH, Martel P, Chaumontet C. Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines. Carcinogenesis. 2004;25:1227–1236. [PubMed]
Eisinger AL, Prescott SM, Jones DA, Stafforini DM. The role of cyclooxygenase-2 and prostaglandins in colon cancer. Prostaglandins Other Lipid Mediat. 2007;82:147–154. [PubMed]
Engelbrecht AM, Mattheyse M, Ellis B, Loos B, Thomas M, Smith R, Peters S, Smith C, Myburgh K. Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell line. Cancer Lett. 2007;258:144–153. [PubMed]
Espìn JC, Garcìa-Conesa MT, Tomás-Barberán FA. Nutraceuticals: facts and fiction. Phytochemistry. 2007;68:2986–3008. [PubMed]
Fuggetta MP, Lanzilli G, Tricarico M, Cottarelli A, Falchetti R, Ravagnan G, Bonmassar E. Effect of resveratrol on proliferation and telomerase activity of human colon cancer cells in vitro. J Exp Clin Cancer Res. 2006;25:189–193. [PubMed]
Giovannucci E. Diet, body weight, and colorectal cancer: a summary of the epidemiologic evidence. J Womens Health (Larchmt) 2003;12:173–182. [PubMed]
Gordaliza M. Natural products as leads to anticancer drugs. Clin Transl Oncol. 2007;9:767–776. [PubMed]
Gossé F, Guyot S, Roussi S, Lobstein A, Fischer B, Seiler N, Raul F. Chemopreventive properties of apple procyanidins on human colon cancer-derived metastatic SW620 cells and in a rat model of colon carcinogenesis. Carcinogenesis. 2005;26:1291–1295. [PubMed]
Grubben MJ, Van Den Braak CC, Broekhuizen R, De Jong R, Van Rijt L, De Ruijter E, Peters WH, Katan MB, Nagengast FM. The effect of unfiltered coffee on potential biomarkers for colonic cancer risk in healthy volunteers: a randomized trial. Department of Aliment Pharmacol Ther. 2000;14:1181–1190. [PubMed]
Gustin DM, Brenner DE. Chemoprevention of colon cancer: current status and future prospects. Cancer Metastasis Rev. 2004;21:323–348.  [PubMed]
Gwak J, Park S, Cho M, Song T, Cha SH, Kim DE, Jeon YJ, Shin JG, Oh S. Polysiphonia japonica extract suppresses the Wnt/beta-catenin pathway in colon cancer cells by activation of NF-kappaB. Int J Mol Med. 2006;17:1005–1010. [PubMed]
Hakkak R, Korourian S, Ronis MJ, Johnston JM, Badger TM. Soy protein isolate consumption protects against azoxymethane-induced colon tumors in male rats. Cancer Lett. 2001;166:27–32. [PubMed]
Hao X, Sun Y, Yang CS, Bose M, Lambert JD, Ju J, Lu G, Lee MJ, Park S, Husain A, Wang S. Inhibition of intestinal tumorigenesis in Apc(min/+) mice by green tea polyphenols (polyphenon E) and individual catechins. Nutr Cancer. 2007;59:62–69. [PubMed]
Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS. Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer. J Surg Res. 2007;143:58–65. [PubMed]
Hong J, Bose M, Ju J, Ryu JH, Chen X, Sang S, Lee MJ, Yang CS. Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase. Carcinogenesis. 2004;25:1671–1679. [PubMed]
Hong MY, Seeram NP, Zhang Y, Heber D. Anticancer effects of Chinese red yeast rice versus monacolin K alone on colon cancer cells. J Nutr Biochem. 2008;19:448–458. [PMC free article] [PubMed]
Hsu YC, Weng HC, Lin S, Chien YW. Curcuminoids-cellular uptake by human primary colon cancer cells as quantitated by a sensitive HPLC assay and its relation with the inhibition of proliferation and apoptosis. J Agric Food Chem. 2007;55:8213–8222. [PubMed]
Humphries A, Wright NA. Colonic crypt organization and tumorigenesis. Nat Rev Cancer. 2008;8:415–424. [PubMed]
Hu R, Khor TO, Shen G, Jeong WS, Hebbar V, Chen C, Xu C, Reddy B, Chada K, Kong AN. Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable. Carcinogenesis. 2006;27:2038–2046.[PubMed]
Hwang JT, Ha J, Park IJ, Lee SK, Baik HW, Kim YM, Park OJ. Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway. Cancer Lett. 2007;247:115–121. [PubMed]
Issa AY, Volate SR, Muga SJ, Nitcheva D, Smith T, Wargovich MJ. Green tea selectively targets initial stages of intestinal carcinogenesis in the AOM-ApcMin mouse model. Carcinogenesis. 2007;28:1978–1984. [PubMed]
Janakiram NB, Cooma I, Mohammed A, Steele VE, Rao CV. Beta-ionone inhibits colonic aberrant crypt foci formation in rats, suppresses cell growth, and induces retinoid X receptor-alpha in human colon cancer cells. Mol Cancer Ther. 2008;7:181–190. [PubMed]
Jain RK. Tumor angiogenesis and accessibility: role of vascular endothelial growth factor. Semin Oncol. 2002;29:3–9. [PubMed]
Jenab M, Thompson LU. Phytic acid in wheat bran affects colon morphology, cell differentiation and apoptosis. Carcinogenesis. 2000;21:1547–1552. [PubMed]
Ju J, Hong J, Zhou JN, Pan Z, Bose M, Liao J, Yang GY, Liu YY, Hou Z, Lin Y, Ma J, Shih WJ, Carothers AM, Yang CS. Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (?)-epigallocatechin-3-gallate, the major catechin in green tea. Cancer Res. 2005;65:10623–10631. [PubMed]
Ju J, Liu Y, Hong J, Huang MT, Conney AH, Yang CS. Effects of green tea and high-fat diet on arachidonic acid metabolism and aberrant crypt foci formation in an azoxymethane-induced colon carcinogenesis mouse model. Nutr Cancer. 2003;46:172–178. [PubMed]
Jung YD, Kim MS, Shin BA, Chay KO, Ahn BW, Liu W, Bucana CD, Gallick GE, Ellis LM. EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells. Br J Cancer. 2001;84:844–850. [PMC free article][PubMed]
Kamaleeswari M, Deeptha K, Sengottuvelan M, Nalini N. Effect of dietary caraway (Carum carvi L.) on aberrant crypt foci development, fecal steroids, and intestinal alkaline phosphatase activities in 1,2-dimethylhydrazine-induced colon carcinogenesis. Toxicol Appl Pharmacol. 2006;214:290–296. [PubMed]
Kang JH, Han IH, Sung MK, Yoo H, Kim YG, Kim JS, Kawada T, Yu R. Soybean saponin inhibits tumor cell metastasis by modulating expressions of MMP-2, MMP-9 and TIMP- 2. Cancer Lett. 2008;261:84–92. [PubMed]
Kaur M, Singh RP, Gu M, Agarwal R, Agarwal C. Grape seed extract inhibits in vitro and in vivo growth of human colorectal carcinoma cells. Clin Cancer Res. 2006;12:6194–6202. [PubMed]
Khor TO, Cheung WK, Prawan A, Reddy BS, Kong AN. Chemoprevention of familial adenomatous polyposis in Apc(Min/+) mice by phenethyl isothiocyanate (PEITC) Mol Carcinog. 2008;47:321–325. [PubMed]
Kumar R. Commentary: targeting colorectal cancer through molecular biology. Semin Oncol. 2005;32:S37–S39. [PubMed]
Kim YS, Milner JA. Dietary modulation of colon cancer risk. J Nutr. 2007;137:2576S–2579S. [PubMed]
Kroll DJ, Shaw HS, Oberlies NH. Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integr Cancer Ther. 2007;6:110–119. [PubMed]
Krzystyniak KL. Current strategies for anticancer chemoprevention and chemoprotection. Acta Pol Pharm. 2002;59:473–478. [PubMed]
Lala G, Malik M, Zhao C, He J, Kwon Y, Giusti MM, Magnuson BA. Anthocyanin-rich extracts inhibit multiple biomarkers of colon cancer in rats. Nutr Cancer. 2006;54:84–93. [PubMed]
Lee HJ, Lee EO, Rhee YH, Ahn KS, Li GX, Jiang C, L? J, Kim SH. An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis. Carcinogenesis. 2006;27:2455–2463. [PubMed]
Li L, Ahmed B, Mehta K, Kurzrock R. Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Mol Cancer Ther. 2007;6:1276–1282. [PubMed]
Lila MA. From beans to berries and beyond: teamwork between plant chemicals for protection of optimal human health. Ann N Y Acad Sci. 2007;1114:372–380. [PubMed]
Lu H, Li J, Zhang D, Stoner GD, Huang C. Molecular mechanisms involved in chemoprevention of black raspberry extracts: from transcription factors to their target genes. Nutr Cancer. 2006;54:69–78. [PubMed]
Luu HH, Zhang R, Haydon RC, Rayburn E, Kang Q, Si W, Park JK, Wang H, Peng Y, Jiang W, He TC. Wnt/beta-catenin signaling pathway as a novel cancer drug target. Curr Cancer Drug Targets. 2004;4:653–671. [PubMed]
Mahmoud NN, Carothers AM, Grunberger D, Bilinski RT, Churchill MR, Martucci C, Newmark HL, Bertagnolli MM. Plant phenolics decrease intestinal tumors in an animal model of familial adenomatous polyposis. Carcinogenesis. 2000;21:921–927. [PubMed]
Manju V, Nalini N. Chemopreventive efficacy of ginger, a naturally occurring anticarcinogen during the initiation, post-initiation stages of 1,2 dimethylhydrazine-induced colon cancer. Clin Chim Acta. 2005;358:60–67. [PubMed]
Manson MM, Farmer PB, Gescher A, Steward WP. Innovative agents in cancer prevention. Recent Results Cancer Res. 2005;166:257–275. [PubMed]
Matsuura N, Miyamae Y, Yamane K, Nagao Y, Hamada Y, Kawaguchi N, Katsuki T, Hirata K, Sumi S, Ishikawa H. Aged garlic extract inhibits angiogenesis and proliferation of colorectal carcinoma cells. J Nutr. 2006;136:842S–846S. [PubMed]
Miyata T. Pharmacological basis of traditional medicines and health supplements as curatives. J Pharmacol Sci. 2007;103:127–131.[PubMed]
Mutch MG. Molecular profiling and risk stratification of adenocarcinoma of the colon. J Surg Oncol. 2007;96:693–703. [PubMed]
Nalini N, Manju V, Menon VP. Effect of spices on lipid metabolism in 1,2-dimethylhydrazine-induced rat colon carcinogenesis. J Med Food. 2006;9:237–245. [PubMed]
Nishino H, Satomi Y, Tokuda H, Masuda M. Cancer control by phytochemicals. Curr Pharm Des. 2007;13:3394–3399. [PubMed]
Niv Y. Microsatellite instability and MLH1 promoter hypermethylation in colorectal cancer. World J Gastroenterol. 2007;13:1767–1769.[PubMed]
Onogi N, Okuno M, Komaki C, Moriwaki H, Kawamori T, Tanaka T, Mori H, Muto Y. Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats. Carcinogenesis. 1996;17:1291–1296. [PubMed]
Papapolychroniadis C. Environmental and other risk factors for colorectal carcinogenesis. Tech Coloproctol. 2004;8 Suppl 1:s7–s9.[PubMed]
Park EJ, Pezzuto JM. Botanicals in cancer chemoprevention. Cancer Metastasis Rev. 2002;21:231–255. [PubMed]
Park JW, Woo KJ, Lee JT, Lim JH, Lee TJ, Kim SH, Choi YH, Kwon TK. Resveratrol induces pro-apoptotic endoplasmic reticulum stress in human colon cancer cells. Oncol Rep. 2007;18:1269–1273. [PubMed]
Patel R, Ingle A, Maru GB. Polymeric black tea polyphenols inhibit 1,2- dimethylhydrazine induced colorectal carcinogenesis by inhibiting cell proliferation via Wnt/beta-catenin pathway. Toxicol Appl Pharmacol. 2008;227:136–146. [PubMed]
Patlolla JM, Raju J, Swamy MV, Rao CV. Beta-escin inhibits colonic aberrant crypt foci formation in rats and regulates the cell cycle growth by inducing p21(waf1/cip1) in colon cancer cells. Mol Cancer Ther. 2006;5:1459–1466. [PubMed]
Porath D, Riegger C, Drewe J, Schwager J. Epigallocatechin-3-gallate impairs chemokine production in human colon epithelial cell lines. J Pharmacol Exp Ther. 2005;315:1172–1180. [PubMed]
Rajakangas J, Misikangas M, Päivärinta E, Mutanen M. Chemoprevention by white currant is mediated by the reduction of nuclear beta-catenin and NF-kappaB levels in Min mice adenomas. Eur J Nutr. 2008;47:115–122. [PubMed]
Raju J, Swamy MV, Cooma I, Patlolla JM, Pittman B, Reddy BS, Steele VE, Rao CV. Low doses of beta-carotene and lutein inhibit A“xOM-induced rat colonic ACF formation but high doses augment ACF incidence. Int J Cancer. 2005;113:798–802. [PubMed]
Reddy BS. Colon carcinogenesis models for chemoprevention studies. Hematol Oncol Clin North Am. 1998;12:963–973. [PubMed]
Reddy BS, Hirose Y, Cohen LA, Simi B, Cooma I, Rao CV. Preventive potential of wheat bran fractions against experimental colon carcinogenesis: implications for human colon cancer prevention. Cancer Res. 2000;60:4792–4797. [PubMed]
Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A, Rath M. In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human colon cancer cell HCT 116 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry. Oncol Rep. 2005;13:421–425. [PubMed]
Rowley PT. Inherited susceptibility to colorectal cancer. Annu Rev Med. 2005;56:539–554. [PubMed]
Sang S, Ju J, Lambert JD, Lin Y, Hong J, Bose M, Wang S, Bai N, He K, Reddy BS, Ho CT, Li F, Yang CS. Wheat bran oil and its fractions inhibit human colon cancer cell growth and intestinal tumorigenesis in Apc(min/+) mice. J Agric Food Chem. 2006;54:9792–9797. [PubMed]
Satia-Abouta J, Galanko JA, Martin CF, Ammerman A, Sandler RS. Food groups and colon cancer risk in African-Americans and Caucasians. Int J Cancer. 2004;109:728–736. [PubMed]
Seeram NP, Adams LS, Zhang Y, Lee R, Sand D, Scheuller HS, Heber D. Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro. J Agric Food Chem. 2006;54:9329–9339. [PubMed]
Sengupta A, Ghosh S, Bhattacharjee S. Dietary cardamom inhibits the formation of azoxymethane-induced aberrant crypt foci in mice and reduces COX-2 and iNOS expression in the colon. Asian Pac J Cancer Prev. 2005;6:118–122. [PubMed]
Sengupta A, Ghosh S, Das S. Modulatory influence of garlic and tomato on cyclooxygenase-2 activity, cell proliferation and apoptosis during azoxymethane induced colon carcinogenesis in rat. Cancer Lett. 2008;208:127–136. [PubMed]
Shimizu M, Deguchi A, Joe AK, Mckoy JF, Moriwaki H, Weinstein IB. EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells. J Exp Ther Oncol. 2005a;5:69–78. [PubMed]
Shimizu M, Deguchi A, Lim JT, Moriwaki H, Kopelovich L, Weinstein IB. (?)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells. Clin Cancer Res. 2005b;11:2735–2746. [PubMed]
Singh RP, Gu M, Agarwal R. Silibinin inhibits colorectal cancer growth by inhibiting tumor cell proliferation and angiogenesis. Cancer Res. 2008;68:2043–2050. [PubMed]
Spychalski M, Dziki L, Dziki A. Chemoprevention of colorectal cancer – a new target needed? Colorectal Dis. 2007;9:397–401. [PubMed]
Sriram N, Kalayarasan S, Ashokkumar P, Sureshkumar A, Sudhandiran G. Diallyl sulfide induces apoptosis in Colo 320 DM human colon cancer cells: involvement of caspase-3, NF-kappaB, and ERK-2. Mol Cell Biochem. 2008;311:157–165. [PubMed]
Su CC, Chen GW, Lin JG, Wu LT, Chung JG. Curcumin inhibits cell migration of human colon cancer colo 205 cells through the inhibition of nuclear factor kappa B /p65 and down-regulates cyclooxygenase-2 and matrix metalloproteinase-2 expressions. Anticancer Res. 2006;26:1281–1288. [PubMed]
Su CC, Lin JG, Li TM, Chung JG, Yang JS, Ip SW, Lin WC, Chen GW. Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3. Anticancer Res. 2006;26:4379–4389. [PubMed]
Taché S, Ladam A, Corpet DE. Chemoprevention of aberrant crypt foci in the colon of rats by dietary onion. Eur J Cancer. 2007;43:454–458. [PubMed]
Tanaka S, Haruma K, Yoshihara M, Kajiyama G, Kira K, Amagase H, Chayama K. Aged garlic extract has potential suppressive effect on colorectal adenomas in humans. J Nutr. 2006;136:821S–826S. [PubMed]
Tessitore L, Davit A, Sarotto I, Caderni G. Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21(CIP) expression. Carcinogenesis. 2000;21:1619–1622. [PubMed]
Tian Y, Song Y. Effects of inositol hexaphosphate on proliferation of HT-29 human colon carcinoma cell line. World J Gastroenterol. 2006;12:4137–4142. [PubMed]
Vainio H, Weiderpass E. Fruit and vegetables in cancer prevention. Nutr Cancer. 2006;54:111–142. [PubMed]
Vincent TL, Gatenby RA. An evolutionary model for initiation, promotion, and progression in carcinogenesis. Int J Oncol. 2008;32:729–737. [PubMed]
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–532. [PubMed]
Walfisch S, Walfisch Y, Kirilov E, Linde N, Mnitentag H, Agbaria R, Sharoni Y, Levy J. Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients. Eur J Cancer Prev. 2007;16:298–303. [PubMed]
Watson JL, Hill R, Lee PW, Giacomantonio CA, Hoskin DW. Curcumin induces apoptosis in HCT-116 human colon cancer cells in a p21-independent manner. Exp Mol Pathol. 2008 (Ahead of print)
Williams MT, Hord NG. The role of dietary factors in cancer prevention: beyond fruits and vegetables. Nutr Clin Pract. 2005;20:451–459.[PubMed]

Zykova TA, Zhu F, Zhai X, Ma WY, Ermakova SP, Lee KW, Bode AM, Dong Z. Resveratrol directly targets COX-2 to inhibit carcinogenesis. Mol Carcinog. 2008 (Ahead of print)

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