Diosmetin Enhances Apoptosis in Thyroid Cancer CAL-62 Cells via Increasing Oxidative Stress and Inhibiting PI3K/AKT/mTOR Pathway

Abstract

Background: Thyroid cancer is a malignancy that arises from the thyroid gland. While it is considered an uncommon condition, cases of thyroid cancer have been steadily rising in recent years worldwide.Objectives: The present work assesses the apoptotic-inducing potential of diosmetin against thyroid cancer cells.Materials and Methods: The impact of diosmetin on the growth of cells was evaluated using the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Apoptosis in the experimental CAL-62 cells was assessed using dual staining and 4′,6-diamidino-2-phenylindole (DAPI) staining. Oxidative stress marker levels were quantified in the cell lysates of CAL-62 cells exposed to diosmetin. PI3K/AKT/mTOR signaling protein levels were also assessed using cell lysates from both control and diosmetin-treated CAL-62 cells.Results: The present results exhibited that diosmetin efficiently decreased the viability of both CAL-62 and BHT-101 cells. Additionally, diosmetin considerably induced apoptosis in CAL-62 cells, as evidenced by the fluorescent staining assay results. Diosmetin treatment remarkably increased TBA reactive species (TBARS) levels and subsequently decreased antioxidant levels in CAL-62 cells. Moreover, diosmetin treatment effectively blocked PI3K/AKT/mTOR signaling in CAL-62 cells.Conclusion: The findings of this work exhibit that diosmetin efficiently inhibits cell proliferation and promotes oxidative stress-mediated apoptosis in thyroid cancer CAL-62 cells. Consequently, it possesses the potential to serve as an anti-cancer agent in treating thyroid cancer.

Keywords: Oxidative stress; thyroid cancer; diosmetin; CAL-62 cells; apoptosis; PI3K/AKT/mTOR pathway