Chemoprevention

Actinic keratoses were the first skin lesions to be treated topically with all-frans-retinoic acid. In various clinical trials, retinoids have been shown to be active in chemoprevention and treatment or prevention skin malignancies [2]. 

Currently, 13-cis-retinoic acid is the most studied chemopreventive agent that decreases the incidence of second primary tumors in patients with head-and-neck cancer, reverses premalignant lesions, and reduces appearance of nonmelanoma skin cancer in patients with xeroderma pigmentosum. Unfortunately, this vitamin A derivative has a significant clinical toxicity, which limits its utility in a practice setting. 

Retinoids, isothiocyanates and tea polyphenols have been identified as possible chemopreventive agents for cancers of the lung and oral cavity. While a number of trials have been conducted with retinoids or (3-carotene, the results were ambiguous and the causes are still being debated. 

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

Abu J, Batuwangala M, Herbert K et al (2005) Retinoic acid and retinoid receptors potential chemopreventive and therapeutic role in cervical cancer. Lancet Oncol 6 712-720... 

Jordan VC (2007) Chemoprevention of breast cancer with selective oestrogen-receptor modulators. Nat Rev Cancer 7 46-53... 

Combs GF, Gray WP Chemopreventive agents—selenium. Pharmacol Ther 1998 79 179. 

LIN J K, CHEN Y c, HUANG Y T and LiN-SHiAU s Y (1997) Snppression of protein kinase C and nuclear oncogene expression as possible molecnlar mechanisms of cancer chemoprevention by apigenin and curciunin Journal Cell Biochemistry Suppl. 28-9, 39-48. 

GREENWALD P, NIXON D W, MALONE W F, KELLOFF G J, STERN H R and WITKIN K M (1990) Concepts in cancer chemoprevention research . Cancer, 65, 1483-90. 

HECHT s s (1999) Chemoprevention of cancer by isothiocyanates, modifiers of carcinogen metabolism , JNutr, 129, 768S-74S. 

HENNEKENS c H, STAMPFER M J and WILLETT w (1984) Micronutrients and cancer chemoprevention . Cancer Detect Prev, 1, 147-58. 

KHACHIK F, BEECHER G R and SMITH J c (1995) Lutein, lycopene, and their oxidative metabolites in chemoprevention of cancer , J Cell Biochem Supp, 22, 236-46. 

PRIMIANO T, EGNER P A, SUTTER T R, KELLOFF G J, ROEBUCK B D and KENSLER T W (1995) Intermittent dosing with oltipraz relationship between chemoprevention of aflatoxin-... 

KASSIE F, PooL-zoBEL B, PARZEFALL w and KNASMULLER s (1999) Genotoxic effects of benzyl isothiocyanate, a natural chemopreventive agent . Mutagenesis, 14 595-604. 

OGAWA K, HIROSE M, SUGIURA S, CUI L, IMAIDA K, OGISO T and SHIRAI T (2001) Dose-dependent promotion by phenylethyl isothiocyanate, a known chemopreventer, of two-stage rat urinary bladder and liver carcinogenesis , Nutr Cancer, 40 134-9. 

CHUNG F L, CONAWAY c c, RAO c V and REDDY B s (2000) Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate . Carcinogenesis, 21 2287-91. 

CHUNG F L, KELLOFF G, STEELE V, PITTMAN B, ZANG E, JIAO D, RIGOTTY J, CHOI C I and RiVENSON A (1996) Chemopreventive efficacy of arylalkyl isothrocyanates and N-acetylcysteine for lung tumorigenesis in Fischer rats . Cancer Res, 56 772-8. 

XU K and thornalley p j (2001) Signal transduction activated by the cancer chemopreventive isothiocyanates cleavage of BID protein, tyrosine phosphorylation and activation of INK , Br J Cancer, 84 670-73. 

GUPTA s, AHMAD N and MUKHTAR H (1999) Prostate cancer chemoprevention by green tea , Semin Urol Oncol, 17, 70-76. 

JAVED s, MEHROTRA N K and SHUKLA Y (1998) Chemopreventive effects of black tea polyphenols in mouse skin model of carcinogenesis , Biomed Environ Sci, 11 (4), 307-13. 

KHAFIF A, SCHANTZ s P, CHOU T c, EDELSTEIN D and SACKS P G (1998) Quantitation of chemopreventive synergism between epigallocatechin gallate and curcumin in normal, premalignant, and malignant oral epithelial cells . Carcinogenesis, 19, 419-24. 

WEISBURGER J H (2001) Chemopreventive effects of cocoa polyphenols of chroitic diseases , Exp Biol Med, 226 (10), 891-7. 

NCI (1996) Clinical Development Plan Genistein. National Cancer Institute (NCI) Chemoprevention Branch and Agent Development Committee. J Cell Biochem. 26S 114-26. 

Chemoprevention and immunocompetence effect of rice bran saccharides (Nakamura, 1992 Miyoshi et al., 2001). 

The First International Symposium on Disease Prevention by IP6 and other Rice Bran Components. was conducted in Kyoto, Japan on June 8-9, 1998. Scientists from all over the globe gathered and presented their research findings on the effect of IP6 and other rice bran components on several aspects of health. The brain storming sessions of nearly 35 presentations demonstrated that IP6 is a chemopreventive agent as both a cancer inhibitor and a cancer suppressor in mammary gland, colon and lung cancer (Shamsuddin et al, 1997). 

Studies by Hudson et al, (2000) have demonstrated the presence of eight polyphenols in rice bran by using high-pressure liquid chromatography. They are protocatechuic acid, p-coumaric acid, ferulic acid, sinapic aci vanillic acid, caffeic acid, which is a methoxycirmamic acid derivative, and tricin. The effect of these polyphenols on cell viability and on the colony-forming ability of human-derived MDA MB 468 and HBL 100 breast cells, colon-derived SW 480 and human colonic epithelial cells was assessed. These authors concluded that rice bran polyphenols have putative cancer chemopreventive properties. 

Tocotrienols are another group of phytochemicals of rice bran which have a chemopreventive effect and have been demonstrated to inhibit breast cancer (Nesaremam et al., 1998). The polysaccharides of rice bran contain a-glucan, the anti-tumor effect of which has been demonstrated by its inhibition of gastrointestinal carcinogenesis (Akeshita et al., 1992). Rice bran agglutinin has been shown to induce apoptosis of cancer cells by the mechanism of cell cycle dysregulation (Miyoshi et al., 2001). 

HUDSON A, DiNH p A, KOKUBUN T, siMMONDS M s, GESCHER A (2000) Characterization of potentially chemopreventive phenols in extracts of brown rice that inhibit the growth of human breast and colon cancer cells. Cancer Epidemiol Biomarkers Prev, 9 (11) 1163-70. 

Dashwood, R.H. et al., Chemopreventive properties of chlorophylls towards aflatoxin Bp A review of the antimutagenicity and anticarcinogenicity data in rainbow trout, Mutat. Res., 399, 245, 1998. 

Ireson, C. et al.. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res., 61, 1058, 2001. 

Konoshima, T. et al.. Cancer chemopreventive activity of an iridoid glycoside, 8-acetylharpagide, fvom Ajuga decumbens. Cancer I tt., 157, 87, 2000. 

Placebo-controlled chemoprevention trial 30 mg/day carotene + 25,000 lU P-Carotene Lung cancer and total mortality + 36... 

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