Taraxasterol Suppresses Renal Cell Carcinoma Progression by Modulating CellCycle Progression and Apoptosis

Introduction: Renal cell carcinoma (RCC) is a common and aggressive urological malignancy with limited response to chemotherapy and radiotherapy. The search for effective, low-toxicity natural compounds is therefore of increasing interest. Taraxasterol (TAX), a pentacyclic triterpene from dandelion, has shown antitumor activity in several cancers, but its effects on RCC remain unexplored. To investigate the antitumor effects and underlying mechanisms of TAX on RCC in vitro and in vivo Methods: The human embryonic kidney cell HEK-293T and human RCC cells (786-O) were cultured and treated with different concentrations of TAX (0, 5, 10, and 15 µM), respectively. Next, the MTT assay was employed for detecting cell viability, the scratch assay for cell migration, the Transwell for cell invasion, flow cytometry for changes in mitochondrial membrane potential, apoptosis levels, and cell cycle, and the western blot for protein expression levels related to cell cycle and apoptosis. Additionally, a 786-O xenograft model was established in BALB/c nude mice to evaluate the in vivo antitumor effect of TAX. Tumor volume and weight were measured, and Ki-67 and cleaved Caspase-3 expression in tumor tissues were assessed via immunohistochemistry Results: TAX did not affect the viability, apoptosis, or cell cycle of HEK-293T cells, but significantly inhibited proliferation, migration, and invasion of 786-O cells, while inducing apoptosis and G2/M arrest in a concentration-dependent manner. TAX reduced mitochondrial membrane potential, increased cleaved-Caspase-3 and cleaved-PARP, decreased Bcl-2, and downregulated Cyclin B1 and CDK1, while upregulating p21 and p27. In vivo, TAX suppressed tumor growth and reduced Ki-67, while increasing cleaved Caspase-3 expression in xenograft tumors. Discussion: These findings support TAX as a promising natural compound for RCC therapy. Further work is needed to validate its effects across additional RCC models and to explore other potential molecular pathways Conclusion: TAX exerts antiproliferative, pro-apoptotic, and anti-invasive effects on RCC, highlighting its potential as a therapeutic candidate.