2. Academic Validation
  3. Flavopiridol induces cell cycle arrest and apoptosis by interfering with CDK1 signaling pathway in human ovarian granulosa cells

Flavopiridol induces cell cycle arrest and apoptosis by interfering with CDK1 signaling pathway in human ovarian granulosa cells

  • Sci Rep. 2024 Oct 31;14(1):26239. doi: 10.1038/s41598-024-77032-2.
Xiao-Zhen Li 1 2,  Wei Song 1 2,  Zheng-Hui Zhao 1,  You-Hui Lu 3,  Gen-Lu Xu 1,  Li-Jia Yang 1 2,  Shen Yin 2,  Qing-Yuan Sun 4,  Lei-Ning Chen 5
Affiliations

Affiliations

  • 1 Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
  • 2 College of Life Sciences, Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao, 266109, China.
  • 3 Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 4 Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China. sunqy@gd2h.org.cn.
  • 5 Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China. ivfboy@189.cn.
PMID: 39482384 DOI: 10.1038/s41598-024-77032-2
Abstract

Several clinical trials have been conducted to evaluate the use of flavopiridol (FP) to treat a variety of cancers, and almost all Cancer drugs were found to be associated with toxicity and side effects. It is not clear whether the use of FP will affect the female reproductive system. Granulosa cells, as the important cells that constitute the follicle, play a crucial role in determining the reproductive ability of females. In this study, we investigated whether different concentrations of FP have a toxic effect on the growth of immortalized human ovarian granulosa cells. The results showed that FP had an inhibitory effect on cell proliferation at a level of nanomole concentration. FP reduced cell proliferation and induced Apoptosis by inducing mitochondrial dysfunction and oxidative stress, as well as increasing Bax/BCL2 and pCDK1 levels. These results suggest that toxicity to the reproductive system should be considered when FP is used in clinical applications.

Keywords

Apoptosis; Cell cycle arrest; Flavopiridol; Human ovarian granulosa cells; Oxidative stress.

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