Cryptolepine-Induced Cell Death ofLeishmania donovaniPromastigotes Is Augmented by Inhibition of Autophagy

[摘要] Leishmania donovaniare the causative agents of visceral leishmaniasis worldwide. Lack of vaccines and emergence of drug resistance warrants the need for improved drug therapy and newer therapeutic intervention strategies against leishmaniasis. In the present study, we have investigated the effect of the natural indoloquinoline alkaloid cryptolepine onL. donovaniAG83 promastigotes. Our results show that cryptolepine induces cellular dysfunction inL. donovanipromastigotes, which leads to the death of this unicellular parasite. Interestingly, our study suggest that cryptolepine-induced cell death ofL. donovaniis counteracted by initial autophagic features elicited by the cells. For the first time, we show that autophagy serves as a survival mechanism in response to cryptolepine treatment inL. donovanipromastigotes and inhibition of autophagy causes an early increase in the amount of cell death. This study can be exploited for designing better drugs and better therapeutic strategies against leishmaniasis in future.

[学科分类] 分子生物学，细胞生物学和基因