ROS-Induced SIRT2 Upregulation Contributes to Cisplatin Sensitivity in Ovarian Cancer

Wenyu Wang; Jihye Im; Soochi Kim; Suin Jang; Youngjin Han; Kyung-Min Yang; Seong-Jin Kim; Danny N Dhanasekaran; Yong Sang Song

doi:10.3390/antiox9111137

ROS-Induced SIRT2 Upregulation Contributes to Cisplatin Sensitivity in Ovarian Cancer

Antioxidants (Basel). 2020 Nov 16;9(11):1137. doi: 10.3390/antiox9111137.

Authors

Wenyu Wang^{1

2}, Jihye Im^{2

3}, Soochi Kim⁴, Suin Jang^{2

3}, Youngjin Han^{2

3}, Kyung-Min Yang⁵, Seong-Jin Kim^{5

6

7}, Danny N Dhanasekaran^{8

9}, Yong Sang Song^{1

2

3

10}

Affiliations

¹ Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul 03080, Korea.
² Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
³ WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 03080, Korea.
⁴ Department of Neurology and Neurological Sciences, Stanford University, School of Medicine, Stanford, CA 94305-5101, USA.
⁵ Precision Medicine Research Center, Advanced Institute of Convergence Technology, Seoul National University, Suwon, Gyeonggi-do 16229, Korea.
⁶ Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Gyeonggi-do 16229, Korea.
⁷ MedPacto Inc., 92, Myeongdal-ro, Seocho-gu, Seoul 06668, Korea.
⁸ Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
⁹ Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
¹⁰ Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea.

Abstract

Cisplatin resistance remains a significant obstacle for improving the clinical outcome of ovarian cancer patients. Recent studies have demonstrated that cisplatin is an important inducer of intracellullar reactive oxygen species (ROS), triggering cancer cell death. Sirtuin 2 (SIRT2), a member of class III NAD⁺ dependent histone deacetylases (HDACs), has been reported to be involved in regulating cancer hallmarks including drug response. In this study, we aimed to identify the role of SIRT2 in oxidative stress and cisplatin response in cancer. Two ovarian cancer cell lines featuring different sensitivities to cisplatin were used in this study. We found different expression patterns of SIRT2 in cisplatin-sensitive (A2780/S) and cisplatin-resistant (A2780/CP) cancer cells with cisplatin treatment, where SIRT2 expression was augmented only in A2780/S cells. Furthermore, cisplatin-induced ROS generation was responsible for the upregulation of SIRT2 in A2780/S cells, whereas overexpression of SIRT2 significantly enhanced the sensitivity of cisplatin-resistant counterpart cells to cisplatin. Our study proposes that targeting SIRT2 may provide new strategies to potentiate platinum-based chemotherapy in ovarian cancer patients.

Keywords: ROS; SIRT2; chemoresistance; cisplatin; ovarian cancer; oxidative stress.

Abstract

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