CD147 Is Involved in Tanshinone IIA-Induced Reprogramming of the Warburg Effect in Prostate Cancer Cells.

Abstract

<p>INTRODUCTION: Cancer cells exhibit metabolic characteristics known as the Warburg effect, which is aerobic glycolysis. Tan IIA, a compound from Salvia miltiorrhiza, has antitumor effects, but its impact on prostate cancer metabolism is not fully understood. METHODS: The effects of Tan IIA on prostate cancer cell proliferation and apoptosis were assessed. Glucose metabolism was evaluated by measuring glycolysis-related metabolic changes and the expression levels of key metabolic enzymes. The underlying molecular mechanisms were investigated by analyzing the AKT/mTOR/ HIF-1α signaling pathway and the role of CD147. RESULTS: Tan IIA significantly suppressed prostate cancer cell proliferation and induced apoptosis by inhibiting glucose metabolism. Treatment with Tan IIA downregulated hypoxia-inducible factor-1α (HIF-1α) expression via blockade of the AKT/mTOR signaling cascade. This resulted in reduced expression levels of critical glycolytic regulators, including glucose transporter 1 (GLUT1), pyruvate kinase M2 (PKM2), and hexokinase 2 (HK2). Furthermore, CD147 silencing impaired glycolysis, an effect potentiated by Tan IIA, suggesting a mechanism involving CD147 inhibition. DISCUSSION: Tan IIA disrupts the glycolytic pathway in prostate cancer cells by suppressing the activity of the AKT/mTOR/HIF-1α axis and potentially through CD147 modulation Conclusion: In summary, these results establish Tan IIA as a potential antitumor compound worthy of further preclinical investigation that exerts its antitumor activity by targeting the unique metabolic dependencies of prostate cancer.</p>