Withaferin-a as a potential candidate for cancer therapy: Experimental evidence of its effects on telomerase plus and minus cancer cells

Abstract

Telomeres (specialized ends of eukaryotic chromosomes) shorten with each round of division in normal human cells. In contrast, cancer cells maintain their telomere length and have been defined as their most consistent attribute. It is achieved by activation of telomere maintenance mechanisms that may either involve up regulation of a specialized reverse transcriptase, telomerase (Telomerase positive, TEP) or recombination based Alternative Lengthening of Telomeres (ALT). Telomere shortening is considered as a tumor suppressor mechanism and hence the drugs to activate this mechanism are deemed anticancer agents. In this chapter we describe the basic mechanisms of telomere length maintenance and their targeting in anticancer therapy. Use of Withaferin-A as a potential anticancer drug for TEP and ALT cells is discussed. Whereas ALT cells escape the deleterious effect of telomerase inhibitors in cancer therapy, Withaferin-A kills both TEP and ALT cells effectively. Thus, Withaferin-A emerges as a promising potential candidate for cancer therapy.