SIRT1 is an actionable target to restore p53 function in HPV-associated cancer therapy.

ABSTRACT:

Background

Our aim was to evaluate the efficacy and anti-cancer action of a precision medicine approach involving a novel SIRT1-dependent pathway that, when disrupted, leads to the restoration of a functional p53 in human papillomavirus (HPV)-transformed cells.

Methods

The anticancer potential of inhibiting SIRT1 was evaluated by examining the effects of the specific SIRT1 inhibitor EX527 (also known as Selisistat) or genetic silencing, either individually or in conjunction with standard chemotherapeutic agents, on a range of HPV⁺ cancer cells and a preclinical mouse model of HPV16-induced cancer.

Results

We show that SIRT1 inhibition restores a transcriptionally active K382-acetylated p53 in HPV⁺ but not HPV^- cell lines, which in turn

SUBMITTER: Lo Cigno I 

PROVIDER: S-EPMC10667542 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature