Xanthohumol Activates Pro-apoptotic Mechanisms in Renal Cancer A498 Cells by Increasing Apoptotic Proteins and Inhibiting PI3K/AKT/mTOR Pathway

ABSTRACT

Background: Kidney cancer, also called renal cancer, is a kind of malignancy that develops in the kidneys. Kidney cancer is a major health issue that has garnered increasing attention in the medical community due to its growing prevalence and complex challenges associated with its treatment. Objectives: The current study evaluated the growth-inhibitory and apoptotic-inducing potentials of xanthohumol against renal cancer A498 cells. Materials and Methods: The cytotoxicity of xanthohumol at varying dosages against kidney cancer A498 cells and nonmalignant Vero cells was studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The accumulation of endogenous reactive oxygen species (ROS) and apoptotic cell death were assessed utilizing their respective fluorescent staining assays. Oxidative stress biomarkers, pro- and anti-apoptotic proteins, cyclin D1, and proteins associated with the PI3K/AKT/mTOR signaling were assessed in the untreated and treated A498 cells using appropriate assay kits. Results: The present results have exhibited that the growth of A498 cells was markedly diminished following treatment with xanthohumol, whereas Vero cell growth remained unaffected by the same concentrations of xanthohumol. The xanthohumol treatment markedly increased ROS generation and promoted apoptosis in A498 cells, which is evidenced by the fluorescent staining results. The xanthohumol treatment increased thiobarbituric acid reactive substances (TBARS) levels and decreased antioxidant levels in A498 cells. Moreover, xanthohumol elevated the pro-apoptotic proteins while diminishing the levels of Bcl-2, cyclin D1, and PI3K/AKT/mTOR proteins in the kidney cancer A498 cells. Conclusion: The findings of this work highlight that xanthohumol considerably inhibits cell proliferation and activates apoptotic mechanisms in kidney cancer A498 cells. Consequently, it possesses effectiveness as an anti-cancer candidate for the treatment of kidney cancer.

KEYWORDS

• Xanthohumol
• renal cancer
• PI3K/AKT/mTOR pathway
• A498 cells
• apoptosis

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• DOI10.1177/09731296251351701Copy

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