Abstract
Purpose: To investigate the effects of zerumbone on cell invasion, epithelial-mesenchymal transition (EMT) and the potential signaling pathway involved in ovarian cancer cells.Methods: Caov-3 cell proliferation was assessed using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) assay. Wound healing assay was used to determine Caov-3 cell migration while cell invasion was evaluated using Transwell assay. Protein expression was determinedby western blot.Results: Cell viability was reduced by 5, 10, 20, and 50 μM zerumbone (p < 0.05) in a concentrationdependent manner while cell migration and invasion were inhibited by 10 and 20 μM zerumbone (p < 0.05). Protein expression levels of E-cadherin and cytoplasm β-catenin were upregulated by zerumbone (p < 0.05) in a concentration-dependent manner. On the other hand, protein expression levels of Ncadherin, vimentin, ZEB1, nuclear β-catenin, and c-Myc were suppressed by zerumbone (p < 0.05) also in a concentration-dependent manner.Conclusion: The results demonstrate that zerumbone inhibits cell proliferation, migration and invasion, but represses the EMT process via inactivation of Wnt/β-catenin signaling pathway.
 Keywords: Zerumbone, Ovarian cancer, Wnt/β-catenin pathway, Epithelial-mesenchymal transition
Highlights
Ovarian cancer is the most aggressive cancer and the fifth leading cause of death from gynecological malignancies among women [1]
After treatment with zerumbone for 24 h, overexpression of E-cadherin was observed in cells treated with 5, 10, 20, and 50 μM zerumbone, and this upregulation of E-cadherin was enhanced in a concentration-dependent manner
The protein expression levels of Ncadherin, vimentin, and zinc-finger E-box-binding 1 (ZEB1) were reduced in cells treated with 5, 10, 20, and 50 μM of zerumbone compared to those treated with vehicle alone, in a concentration-dependent manner (Figure 3)
Summary
Ovarian cancer is the most aggressive cancer and the fifth leading cause of death from gynecological malignancies among women [1]. Targeting the Wnt/β-catenin pathway may be effective in the treatment of ovarian cancer. By targeting the TGF-β1 signaling pathway, zerumbone was shown to repress the tumorigenicity and mobility of triplenegative breast cancer cells [15]. The goal of this investigation was to investigate the effects of zerumbone on cell invasion and the EMT and to elucidate the potential signaling pathway involved in Caov-3 cells, a human ovarian cancer cell line. After treatment with zerumbone for 24 h, RIPA cell lysis buffer (Beyotime, China) and BCA Protein Assay Kit (Abcam, UK) were used to extract proteins and measure the protein concentration, respectively.
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