Isothiocyanate Iberin inhibits cell proliferation and induces cell apoptosis in the progression of ovarian cancer by mediating ROS accumulation and GPX1 expression

  • Biomed Pharmacother. 2021 Oct;142:111533. doi: 10.1016/j.biopha.2021.111533.
Ting-Ting Gong  1 ,  Qian Guo  1 ,  Xiao Li  1 ,  Tie-Ning Zhang  2 ,  Fang-Hua Liu  3 ,  Xin-Hui He  3 ,  Bei Lin  4 ,  Qi-Jun Wu  5
Affiliations
  • 1. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
  • 2. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
  • 3. Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
  • 4. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China. Electronic address: [email protected].
  • 5. Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China. Electronic address: [email protected].
PMID: 34148735 DOI: 10.1016/j.biopha.2021.111533
Abstract

Ovarian Cancer (OC) is one of the most common gynecologic malignancies with poor survival rate, and Iberin is a member of isothiocyanate family with anti-tumor activity. However, the role of Iberin in OC development has not been reported yet. In this study, A2780 and OVCAR-3 cells were treated with gradient concentrations of Iberin to investigate the effect of Iberin on OC in vitro. Meanwhile, the in vivo tumorgenesis experiment was performed using female BALB/c nude mice treated with Iberin. Iberin inhibited cell proliferation, induced G2 cell cycle arrest and promoted cell Apoptosis in OC cells. Besides, Iberin reduced GSH/GSSG level, enhanced ROS accumulation, and activated MAPK signaling in OC cells. More interestingly, ROS scavenger (NAC) compensated the anti-proliferative and pro-apoptotic effects of Iberin on OC cells, suggesting the involvement of ROS in the regulation of Iberin on OC cell growth. Notably, Iberin induced down-regulation of glutathione peroxidase-1 (GPX1), and over-expression of GPX1 reversed Iberin-mediated alterations in the proliferation, Apoptosis and ROS accumulation of OC cells. The in vivo tumorgenesis study further evidenced the protection of Iberin against OC development. Besides, Iberin displayed a synergistic effect on the enhancement of chemo-sensitivity in OC cells. In summary, our study demonstrates the anti-tumor effect of Iberin on OC and its potential as a therapeutic agent against OC in the future.

Keywords
Apoptosis; Cell proliferation; GPX1; Iberin; Ovarian cancer; ROS accumulation.
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