Cancer chemopreventive activities

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. 

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

In addition to their possible prooxidant activity (see above) polyphenols and flavonoids may influence cancer cells via their antioxidant properties. Recently, Jang et al. [219] studied cancer chemopreventive activity of resveratrol, a natural polyphenolic compound derived from grapes (Chapter 29). These authors showed that resveratrol inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. Flavonoids silymarin and silibinin also exhibited antitumor-promoting effects at the stage I tumor promotion in mouse skin [220] and manifested antiproliferative effects in rat prostate cancer cells [221]. 

Fahmy H, Khalifa S, KonoshtmaT, Zjawiony JK, Potent cancer chemopreventive activity, Marine Drugs 2 1—7, 2002. 

Several studies have shown the ability of DNMT inhibitors to prevent cancer using different pathways [101-104]. Genistein demonstrated cancer chemopreventive activities in animal models [105]. It has been studied in different cancer cell lines and inhibition of cancer cell growth has been shown [106]. But several mechanisms, such as antihormonal effects, are discussed to explain this activity and the exact contribution of DNMT inhibition to in-vivo activity in cancer chemoprevention remains to be determined. 

Ito, C. et al., Chemical constituents of Millettia taiwaniana structure elucidation of five new isoflavonoids and their cancer chemopreventive activity. Journal of Natural Products, 67, 1125, 2004. 

Lambert JD, Yang CS. Cancer chemopreventive activity and bioavailability of tea and tea polyphenols. Mutat Res 2003 523-524 201-208. 

Structures of compounds with potential cancer chemopreventive activity. 

Using the technique of activity-guided chromatographic isolation, it is possible to generate many structurally novel bioactive plant secondary metabolites, and examples have been provided in this chapter of plant secondary metabolites with potential anticancer or potential cancer chemopreventive activity, comprised by compounds representative of the chal-cone, flavanone, flavone, furocoumarin, isoflavone, lignan, oligostilbenoid (resveratrol... 

G., Moon, R. C., and Pezzuto, J. M., 1997, Cancer chemopreventive activity of resveratrol, a natural product derived lfom grapes, Science 275 218-220. 

Itoigawa, M., Ito, C., Tokuda, H., Enjo, F., Nishino, H. and Furukawa, H. (2004) Cancer chemopreventive activity of phenylpropanoids and phytoquinoids from lllicium plants. Cancer Letters 214(2), 165-1 69. 

Wu et al., 2005). Atrovirisidone B isolated from G. atroviridis showed cytotoxic activity against human breast, prostate and large cells. Cancer chemopreventive activity was exhibited by G. assugu plants (Ito et al., 2003a) and also by G. fusca plants (Ito et al., 2003b). 

Fig. 2.8 Chemical structures of alkaloids with promising cancer chemopreventive activity.

Cooke, D., Steward, W.P. Gescher, A.J. Marczylo, T. 2005. Anthocyanins from fruits and vegetables - does bright color signal cancer chemopreventive activity Eur. J. Cancer 41 1931-1940. 

Most tea polyphenols with cancer chemopreventive activities possess antioxidant activity it shonld be emphasized that in addition to acting as ROS scavengers, these componnds can act through multiple mechanisms to modulate the functions of... 

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