Chemopreventive agent

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. 

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

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

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). 

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. 

Chearwae, W. et al.. Modulation of the function of the multidrug resistance-linked ATP-binding transporter ABCG2 by the cancer chemopreventive agent curcumin. Mol. Cancer Then, 5, 1995, 2006. 

Since most cancers are not curable in advanced stages, cancer prevention is an important avenue of exploration. Both lifestyle modifications and chemoprevention agents ultimately may reduce the risk of developing cancer. 

The agent currently being used clinically as a breast cancer chemoprevention agent is tamoxifen. In randomized trials of tamoxifen as an adjuvant treatment for breast cancer, women who received tamoxifen also were found to have a reduced incidence of contralateral primary breast carcinomas.16 A... 

Calcium supplementation appears to be associated with a moderate reduction in risk of recurrent colorectal adenomas, with prospective studies demonstrating a nonstatistical decrease in adenoma recurrence, and the role of calcium as a chemoprevention agent remains under investigation.47... 

Additional agents, including selenium, folic acid, and HMG-CoA reductase inhibitors (statins), show promise as chemopreventive agents in colon cancer, and preliminary and confirmatory studies evaluating their effectiveness have been completed or are ongoing, although none of these agents have been approved for the prevention of colon cancer.46... 

There are no currently recommended prostate cancer chemoprevention agents. 

Verschoyle R D, Greaves P, Cai H, Borkhardt A, Broggini M, D Incalci M, Ricci E, Doppalapudi R, Kapetanovic I M, Steward W P and Gescher A J (2005), Preliminary safety evaluation of the putative cancer chemopreventive agent tricin, a naturally occurring flavone , Cancer Chem Pharmacol, 57, 1-6. 

Boone CW, Kelloff GJ and Maolone WE. 1990. Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials a review. Cancer Res 50 2-9. 

Thomasset SC, Berry DP, Garcea G, Marczylo T, Steward WP and Gescher AJ. 2006. Dietary polyphe-nolic phytochemicals—promising cancer chemopreventive agents in humans A review of their clinical properties. Int J Cancer 120(3) 451-458. 

There are numerous other polyphenolic compounds possessing in vitro and in vivo antioxidative activity. Several examples of these compounds are cited below. One of nonflavonoid polyphenols of particular interest is resveratrol (3,5,4 -trihydroxy-Znmv-stilbcne, Figure 29.8), which has been identified as a potential cancer chemopreventive agent and an antimutagen [182]. It has been found that resveratrol is the efficient inhibitor of cyclooxygenase and the inhibitor of free radical-mediated cellular processes. For example, resveratrol is a better free radical scavenger than a-tocopherol or ascorbic acid but has nearly the same activity as... 

It has been suggested that tamoxifen, one of the most effective therapeutic and chemopreventive agent for breast cancer, modulates protein kinase C through oxidative stress in breast cancer cells [194], Unfortunately, most breast cancers initially responsive to tamoxifen treatment later become resistant. Schiff et al. [195] suggested that the conversion of breast tumors to a tamoxifen-resistant phenotype is associated with oxidative stress and depends on significantly enhanced SOD activity in tumors. 

J. D. Martinez, E. D. Stratagoules, J. M. LaRue, A. A. Powell, P. R. Gause, M. T. Craven, C. M. Payne, M. B. Powell, E. W. Gerner and D. L. Earnest, Different bile acids exhibit distinct biological effects the tumour promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation, Nutr. Cancer, 1998, 31(2), 111. 

Anti-neoplastic activity of UDCA was demonstrated first in the context of ulcerative colitis-associated colorectal carcinogenesis. Subsequently, encouraging (but not definitive) results have been obtained in clinical trials of UDCA for prevention of sporadic colorectal adenoma recurrence, which should prompt further evaluation of UDCA for polyp prevention, particularly given its excellent safety profile compared with other candidate chemoprevention agents such as the nonsteroidal anti-inflammatory drugs. 

D. S. Pardi, E. V. Loftus, W. K. Kremers, J. Keach and K. Lindor, Ursodeoxycholic acid acts as a chemopreventive agent in patients with primary sclerosing cholangitis, Gastroenterology, 2001, 121, 900. 

Li Y, Li X, Guo B. (2010) Chemopreventive agent 3,3 -diinolylmethane selectively induces proteasomal degradation of class 1 histone deacetylases. Cancer Res 70 646-654. 

Soriano AF, Helfrich B, Chan DC, et al. Synergistic effects of new chemopreventive agents and conventional cytotoxic agents against human lung cancer cell lines. Cancer Res 1999 59 6178-6184. 

Cyclin D1/2 expression. Smoke, administered to male strain A/J mice fed a diet with chemopreventive agents, produced a decrease in cyclin Dl/2 expression. Expression of cyclin may be a useful marker in the identification of chemopreventive agents from tobacco smoke . 

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