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

•SIRT1 regulates autophagy by deacetylation of ATGs and transcription factors.•SIRT1 orchestrates ACD by activating bulk autophagy and disrupted lysosomal pool.•SIRT1 modulators inducing ACD can be the future generation chemo-preventives. Cellular localization and deacetylation activity of sirtuin 1...

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Published in:Drug discovery today 2023-09, Vol.28 (9), p.103692-103692, Article 103692
Main Authors: Patra, Srimanta, Praharaj, Prakash P., Singh, Amruta, Bhutia, Sujit K.
Format: Article
Language:English
Subjects:
Apoptosis
Autophagic cell death
Autophagy
Cancer
SIRT1
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Summary:•SIRT1 regulates autophagy by deacetylation of ATGs and transcription factors.•SIRT1 orchestrates ACD by activating bulk autophagy and disrupted lysosomal pool.•SIRT1 modulators inducing ACD can be the future generation chemo-preventives. 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.
ISSN:1359-6446
1878-5832
DOI:10.1016/j.drudis.2023.103692