Effects of Celastrol on the Proliferation and Apoptosis of Prostate Cancer Cells and Its Molecular Mechanism

Abstract

Background: Prostate cancer (PCa) is a significant health concern, and novel therapeutic approaches are needed. Celastrol, a natural compound, has shown promising anticancer effects in various cancer types. However, its regulatory effects on prostate cancer cells and the underlying molecular mechanisms remain unclear. This study aims to understand the regulatory effect of celastrol on the proliferation and apoptosis of prostate cancer cells. Methods: In this study, a nude mouse tumorigenesis model was established by subcutaneously implanting human prostate cancer cell suspension. Celastrol low (0.25 mg/kg), medium (1 mg/kg) and high (4 mg/kg) dose groups were administered by gavage once every three days. The tumor growth trend and tumor inhibition rate were detected. The 5-ethynyl-2-deoxyuridine (EdU) staining was used to detect cell proliferation after treatment with different concentrations of celastrol. qPCR, western blot and co-precipitation experiments were used to explore the molecular mechanism of celastrol on the proliferation and apoptosis of prostate cancer cells. Results: Celastrol medium and high dose groups can effectively inhibit tumor proliferation in nude mice. As the dose increased, the anti-tumor effect increased. The expression of Ki67 and B-cell lymphoma/leukemia-2 (BCL-2) gene in prostate cancer cells can be significantly reduced by celastrol (p < 0.001), and the expression level was decreased in a dose-dependent manner. Meanwhile, prostate cancer cell proliferation was inhibited (p < 0.001). Moreover, the intervention of celastrol inhibits the migration of prostate cancer cells and significantly up-regulates the expression of tumor protein p73 (TP73) (p < 0.001), and the celastrol high-dose group had the best effect. A co-precipitation test found that celastrol can bind to TP73 protein. Overexpression of TP73 reduces the proliferation of prostate cancer cells, while the opposite effect was found when silencing TP73 (p < 0.001). Conclusion: Celastrol inhibits the proliferation and migration of prostate cancer cells and promotes apoptosis by up-regulating the expression of the TP73 protein. This study provides a research basis for the treatment of prostate cancer and the application of celastrol.