Astragalus polysaccharides sensitize ovarian cancer stem cells to PARPi by inhibiting mitophagy via PINK1/Parkin signaling

Qiaohua Peng; Yan Yu; Lele Ye; Songfa Zhang; Yang Li; Xiaoping Hua; Shizhen Shen; Dongxiao Hu; Weiguo Lu

doi:10.1016/j.isci.2024.110376

Astragalus polysaccharides sensitize ovarian cancer stem cells to PARPi by inhibiting mitophagy via PINK1/Parkin signaling

iScience. 2024 Jun 27;27(8):110376. doi: 10.1016/j.isci.2024.110376. eCollection 2024 Aug 16.

Authors

Qiaohua Peng¹, Yan Yu¹, Lele Ye¹, Songfa Zhang¹, Yang Li^{1

2}, Xiaoping Hua¹, Shizhen Shen², Dongxiao Hu¹, Weiguo Lu^{1

2

3}

Affiliations

¹ Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.
² Zhejiang Key Laboratory of Maternal and Infant Safety, Women's Hospital School of Medicine Zhejiang University, Hangzhou 310000, China.
³ Zhejiang Privincial Clinical Research Center for Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China.

Abstract

Ovarian cancer (OC) remains the most lethal gynecological malignant tumor. PARP inhibitors (PARPi) have significantly improved survival, particularly in patients with OC with BRCA1/2 mutations. However, the majority of patients eventually develop resistance to PARPi. Cancer stem cells (CSCs) are considered the source of drug resistance in cancer. Our study found that the synergistic effect of astragalus polysaccharides (APSs) and PARPi was observed in ovarian cancer stem cells (OCSCs) by decreasing cell viability and self-renewal potential while inducing apoptosis. The present study also demonstrated that OCSCs had increased mitophagy. Furthermore, it was observed that APS in combination with PARPi inhibits mitophagy and downregulates the PINK1 protein level in OCSCs. The overexpression of PINK1 via the pEGFP(+)-PINK1 plasmid resulted in a partial reversal of the increased susceptibility of OCSCs when PARPi were administrated concurrently with APS. In conclusion, APS increases OCSC sensitivity to PARPi by inhibiting mitophagy via the PINK1/Parkin pathway regulation.

Keywords: Biological sciences; Cancer; Molecular biology.