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.

Microsoft PowerPoint - NIHMS82721-figure-Figure

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
?PCNA
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.


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