1. Academic Validation
  2. Synergistic antitumor effects of Peiminine and Doxorubicin on breast cancer through enhancing DNA damage via ZEB1

Synergistic antitumor effects of Peiminine and Doxorubicin on breast cancer through enhancing DNA damage via ZEB1

  • Biomed Pharmacother. 2024 Mar 2:173:116353. doi: 10.1016/j.biopha.2024.116353.
Jiajin Xu 1 Zeyi Zhang 1 Hongtao Hu 1 Yaqin Yang 1 Chenghong Xiao 2 Luyi Xi 1 Jiahui Lu 1 Shasha Tian 3 Huajun Zhao 4
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China.
  • 2 Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, China.
  • 3 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China. Electronic address: tss@zcmu.edu.cn.
  • 4 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 311402, China; Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Binwen Rd., Hangzhou, Zhejiang 310053, China. Electronic address: zhj@zcmu.edu.cn.
Abstract

Peiminine, the primary biologically active compound from Fritillaria thunbergii Miq., has demonstrated significant pharmacological activities. Doxorubicin is one of the most potent chemotherapeutic agents for breast Cancer (BC). This study was designed to investigate the efficacy and underlying mechanisms of Peiminine combined with Doxorubicin in treating BC. Our results demonstrated that the combination of Peiminine and 1 mg/kg Doxorubicin exhibited more significant suppression of tumor growth compared with the monotherapy in MDA-MB-231 xenograft nude mice model, which is comparable to the effect of 3 mg/kg Doxorubicin in vivo. Notably, the 3 mg/kg Doxorubicin monotherapy resulted in organ toxicity, specifically in the liver and heart, whereas no toxicity was observed in the combination group. In vitro, this combined treatment exhibited a synergistic reduction on the viability of BC cells. Peiminine enhanced the cell cycle arrest and DNA damage induced by Doxorubicin. Furthermore, the combination treatment effectively blocked DNA repair by inhibiting the MAPKs signaling pathways. And ZEB1 knockdown attenuated the combined effect of Peiminine and Doxorubicin on cell viability and DNA damage. In conclusion, our study found that the combination of Peiminine and Doxorubicin showed synergistic inhibitory effects on BC both in vivo and in vitro through enhancing Doxorubicin-induced DNA damage. These findings support that their combination is a novel and promising therapeutic strategy for treating BC.

Keywords

Breast cancer; DNA damage; Doxorubicin; Peiminine; Synergistic antitumor; ZEB1.

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