Telomerase inhibitors in anticancer therapy: gossypol as a potential telomerase inhibitor

Telomerase is a reverse transcriptase which helps to stabilize the length of telomeres by adding TTAGGG repeats onto the telomeres that enables unlimited division of the cell. Absence of telomerase activity causes replication senescence and cell death. Activity of telomerase was detected in embryonal, gonadal and cancer cells, but was not detected in adult somatic tissues with the exception of tissues containing stem cells. Telomerase inhibitors are being considered as potential anticancer drugs with the hope that the lack of telomerase expression in normal somatic cells would result in a higher specific therapy with fewer side effects than conventional chemotherapy. Because of high activity of telomerase in gonadal cells, we hypothesized that one of the drugs which selectively interfere with spermatogenesis may act like a telomerase inhibitor. Gossypol is a male contraceptive derived from cotton seeds. It causes suppression of spermatogenesis by an unknown mechanism. It has a non-endocrine inhibiting effect on spermatogenesis, gradual onset of action, and irreversible suppression of spermatogenesis with increasing length of use. It also has an antiproliferative effect on cell lines derived from tumors, mild antineoplastic action in vivo with few side effects. It has mild inhibiting influence on the replication of HIV via possible inhibition of reverse transcriptase HIV. This shows its possible telomerase inhibiting activity. It appears that gossypol is a potential new drug for testicular cancer therapy, because of its spermatotoxic and cytotoxic activity on cell lines derivided from testicular tumors. We posit that the use of gossypol in combination with other anticancer chemotherapeutics can lead to a more effective therapy of human tumors. (Ref. 47.).