Gaillardin Impedes Human Ovarian Cancer Metastasis by Acting on Epithelial-Mesenchymal Transition and Angiogenic Factors

Background and objectives: Ovarian cancer is the seventh most frequent cancer and the fifth most common cause of death in women in the world. Gaillardin is a sesquiterpene lactone with anti-cancer effects on different cancer cell lines. This study was conducted to explore the cytotoxic effect of gaillardin on the ovarian cancer cell line SKOV3. Methods: The proliferation rate of SKOV3 cells was assayed using the MTT method and IC50 values were calculated. Migratory and invasiveness of SKOV3 cells following gaillardin treatment were assessed by wound scratch assay. The real-time PCR method was used to measure the mRNA expression of epithelial-mesenchymal transition (EMT) markers CDH1, CDH2, VIM, and FN1 together with angiogenesis markers VEGFA and THBS1. The protein expression of E-cadherin, N-cadherin, vimentin, fibronectin 1, VEGFA, and thrombospondin 1 was measured using western blotting. Results: Gaillardin significantly attenuated the proliferation of SKOV3 cells compared with the controls. Also, the gaillardin-treated cells showed lower invasiveness and migratory properties in comparison to the untreated cells. The results of real-time PCR analysis unraveled that gaillardin treatment significantly upregulated the expression of CDH1 and THBS1 but downregulated CDH2, VIM, FN1, and VEGFA gene levels. This compound also had the same effect on the protein expression of these markers. Conclusion: Regarding the present data affirms that gaillardin may act as a candidate to suppress the proliferation and metastasis in ovarian cancer cells. The mechanisms of the anti-metastatic activities of gaillardin may involve both EMT and angiogenesis cascades.