Targeting SIRT1-regulated autophagic cell death as a novel therapeutic avenue for cancer prevention

Abstract

Cellular localization and deacetylation activity of sirtuin 1 (SIRT1) has a significant role in cancer regulation. The multifactorial role of SIRT1 in autophagy regulates several cancer-associated cellular phenotypes, aiding cellular survival and cell death induction. SIRT1-mediated deacetylation of autophagy-related genes (ATGs) and associated signaling mediators control carcinogenesis. The hyperactivation of bulk autophagy, disrupted lysosomal and mitochondrial biogenesis, and excessive mitophagy are key mechanism for SIRT1-mediated autophagic cell death (ACD). In terms of the SIRT1-ACD nexus, identifying SIRT1-activating small molecules and understanding the possible mechanism triggering ACD could be a potential therapeutic avenue for cancer prevention. In this review, we provide an update on the structural and functional intricacy of SIRT1 and SIRT1-mediated autophagy activation as an alternative cell death modality for cancer prevention.

Keywords: Apoptosis; Autophagic cell death; Autophagy; Cancer; SIRT1.