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A radical approach to cancer.

Undurti Das

Med Sci Monit 2002; 8(4): RA79-92

ID: 420857

Reactive oxygen species are known to be potentially dangerous, but arealso needed for signal-transduction pathways. Tumor cells have relatively low amounts of superoxide dismutase(SOD), which quenches superoxide anion (O2(-*)), and as a result of a higher level of aerobic metabolism,higher concentrations of O2(-*) , compared to normal cells. But this may not be true of all tumor cells.Some tumor cells have relatively higher amounts of vitamin E, a potent anti-oxidant, and a higher levelof anaerobic metabolism, resulting in a balance that is tilted more towards higher anti-oxidant capacity.In both instances of higher aerobic and anaerobic metabolism methods designed to augment free radicalgeneration in tumor cells can cause their death. It is suggested that free radicals and lipid peroxidessuppress the expression of Bcl-2, activate caspases and shorten telomere, and thus inducing apoptosisof tumor cells. Ionizing radiation, anthracyclines, bleomycin and cytokines produce free radicals andthus are useful as anti-cancer agents. But they also produce many side-effects. 2-methoxyoestradiol andpolyunsaturated fatty acids (PUFAs) inhibit SODs and cause an increase of O2(-*) in tumor cells leadingto their death. In addition, PUFAs (especially gamma-linolenic acid), 2-methoxyoestradiol and thalidomidemay possess anti-angiogenic activity. This suggests that free radicals can suppress angiogenesis. Limitedclinical studies done with gamma-linolenic acid showed that it can regress human brain gliomas withoutany significant side-effects. Thus, PUFAs, thalidomide and 2-methoxyoestradiol or their derivatives mayoffer a new radical approach to the treatment of cancer.

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