Induction of SIRT1 and SIRT3 confers resistance to genotoxic apoptosis in thyroid cancers

Abstract

Introduction: Sirtuin is NAD+ dependent deacetylase, which plays great roles on gene silencing, DNA repair and apoptosis. The aim of study is to investigate whether the genotoxic stress such as etoposide treatment is able to induce SIRT1 and SIRT3 in thyroid cancer cell lines and to determine the effect of SIRT1 and SIRT3 induction on programmed cell death provoked by etoposide treatment and to determine the change of the apoptosis related genes ( p53, p21, Bcl-xL and Bax ).Materials and Methods: Protein expression, apoptosis rate, cell viability and mRNA expression of SIRT1, SIRT3 and apoptosis related genes ( Bax, Bcl-xL, p53, p21) were assessed in three thyroid cancer cell lines ( TPC-1, FTC-133 and FRO ) treated with 200 μM etoposide.Results: In western blot, protein induction of SIRT1 and SIRT3 was increased in TPC-1 and decreased in FTC-133 and FRO cell lines. FTC-133 and FRO cells showed significantly increased levels of apoptosis compared with TPC-1 cell via FACS analysis. In RT-PCR, only p21 expression was elevated in TPC-1 and Bax was highly elevated in FTC-133. In FRO, expression of all apoptosis related genes were decreased. Conclusion: The SIRT1 and SIRT3 inducibility by etoposide was also different in thyroid cancer cell lines. The ability to survive under the genotoxic stress was observed accordingly with SIRT1 and SIRT3 inducibility. In addition, SIRT1-Foxp3 signal might be involved in generation of resistance against genotoxic stress. Finally, the emerging role of p21 under genotoxic stress should be addressed in future studies to develop new drug target of thyroid cancer. SIRT1 and SIRT3 might confer the prerequisite resistance to genotoxic drug induced apoptosis.