1. Academic Validation
  2. Pimavanserin tartrate induces apoptosis and cytoprotective autophagy and synergizes with chemotherapy on triple negative breast cancer

Pimavanserin tartrate induces apoptosis and cytoprotective autophagy and synergizes with chemotherapy on triple negative breast cancer

  • Biomed Pharmacother. 2023 Oct 11:168:115665. doi: 10.1016/j.biopha.2023.115665.
Yiqian Zhang 1 Qianrui Huang 1 Qisi Xu 2 Chengsen Jia 1 Yong Xia 3
Affiliations

Affiliations

  • 1 Department of Rehabilitation Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 2 School of Food and Bioengineering, Xihua University, Chengdu 610041, China.
  • 3 Department of Rehabilitation Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Rehabilitation Medicine in Sichuan Province/Rehabilitation Medicine Research Institute, Chengdu 610041, China. Electronic address: yxia4@scu.edu.cn.
Abstract

Triple negative breast Cancer (TNBC) poses a significant clinical challenge due to its lack of targeted therapy options and the frequent development of chemotherapy resistance. Metastasis remains a primary cause of mortality in late-stage TNBC patients, underscoring the urgent need for alternative treatments. Repurposing existing drugs offers a promising strategy for the discovery of novel therapies. In this study, we investigated the potential of pimavanserin tartrate (PVT) as a treatment for TNBC. While previous studies have highlighted PVT's Anticancer effects in various Cancer types, its activity in TNBC remains unclear. Our investigation aimed to elucidate the Anticancer effects and underlying mechanisms of PVT in TNBC. We evaluated the impact of PVT and combination treatments involving PVT on TNBC cell viability, Apoptosis, Autophagy, and associated signaling pathways. Our findings revealed that PVT may induce mitochondria-dependent intrinsic Apoptosis and caused cytoprotective Autophagy via the PI3K/Akt/mTOR pathway in TNBC cells in vitro. Notably, our study demonstrated strong synergistic anti-TNBC effects when combining PVT with doxorubicin. We also found PVT showed some efficacies to inhibit TNBC tumor growth in vivo. These results provided valuable insights into the potential of PVT as an anti-TNBC therapeutic and a possible option for enhancing the sensitivity of TNBC cells to conventional chemotherapy drugs. Further studies are needed to determine the activity and mechanism of PVT in inhibiting TNBC.

Keywords

Chemotherapy; Combination therapy; PI3K/Akt/mTOR pathway; Pimavanserin tartrate; Triple negative breast cancer.

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