The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo

Zohreh Salari, Ahmad Khosravi, Elham Pourkhandani, Elaheh Molaakbari, Ehsan Salarkia, Alireza Keyhani, Iraj Sharifi, Hadi Tavakkoli, Samira Sohbati, Shahriar Dabiri, Guogang Ren, Mohammad Shafie’ei

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Abstract

Background: Epithelial ovarian cancer is very common in women and causes hundreds of deaths per year worldwide. Chemotherapy drugs including cisplatin have adverse effects on patients’ health. Complementary treatments and the use of herbal medicines can help improve the performance of medicine. 6-Gingerol is the major pharmacologically active component of ginger. In this study, we compared the effects of 6-gingerol, cisplatin, and their combination in apoptotic and angiogenetic activities in silico, in test tubes, and in in vivo assays against two ovarian cancer cell lines: OVCAR-3 and human umbilical vein endothelial cells (HUVECs). Methods: The drug-treated cell lines were evaluated for their cytotoxicity, cell cycle, and apoptotic and angiogenetic gene expression changes.

Results: The proportion of apoptosis treated by 6-gingerol coupled with cisplatin was significantly high. In the evaluation of the cell cycle, the combination therapy also showed a significant promotion of a higher extent of the S sequence. The expression of p53 level, Caspase-8, Bax, and Apaf1 genes was amplified again with combination therapy. Conversely, in both cell lines, the cumulative drug concentrations reduced the expression of VEGF, FLT1, KDR, and Bcl-2 genes. Similarly, in the control group, combination treatment significantly decreased the expression of VEGF, FLT1, KDR, and Bcl-2 genes in comparison to cisplatin alone.

Conclusions: The findings of the present study demonstrated that the cisplatin and 6-gingerol combination is more effective in inducing apoptosis and suppressing the angiogenesis of ovarian cancer cells than using each drug alone.
Original languageEnglish
Article number1098429
Pages (from-to)1-17
Number of pages17
JournalFrontiers in Oncology
Volume13
Early online date3 Mar 2023
DOIs
Publication statusPublished - 3 Mar 2023

Keywords

  • Oncology
  • ovarian neoplasm
  • gingerol
  • cisplatin
  • apoptosis
  • angiogenesis
  • molecular dynamics simulation
  • chick embryo

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