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CD147 Is Involved in Tanshinone IIA-Induced Reprogramming of the Warburg Effect in Prostate Cancer Cells
Yunye Wang1, Jierui Zhao2, Shutong Chen3
1Department of Biochemistry, Basic Medical College of Jilin Medical University; Jilin 132013, P.R. China.
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.
Insights
Tan IIA, a compound from Salvia miltiorrhiza, inhibits prostate cancer cell growth by targeting aerobic glycolysis. It disrupts the AKT/mTOR/HIF-1α pathway and potentially CD147, offering a new avenue for cancer treatment.
Area of Science:
- Oncology
- Cancer Metabolism
- Molecular Pharmacology
Background:
- Cancer cells exhibit altered metabolism, specifically the Warburg effect (aerobic glycolysis).
- Tan IIA, a compound from Salvia miltiorrhiza, has demonstrated antitumor properties.
- The precise impact of Tan IIA on prostate cancer metabolism remains incompletely understood.
Purpose of the Study:
- To investigate the effects of Tan IIA on prostate cancer cell proliferation and apoptosis.
- To elucidate the impact of Tan IIA on glucose metabolism and key metabolic enzymes in prostate cancer.
- To explore the molecular mechanisms underlying Tan IIA's action, focusing on the AKT/mTOR/HIF-1α pathway and CD147.
Main Methods:
- Assessed prostate cancer cell proliferation and apoptosis following Tan IIA treatment.
- Evaluated glucose metabolism by measuring glycolysis-related changes and key enzyme expression.
- Investigated molecular mechanisms via analysis of the AKT/mTOR/HIF-1α signaling pathway and CD147 role.
Main Results:
- Tan IIA significantly inhibited prostate cancer cell proliferation and induced apoptosis by suppressing glucose metabolism.
- Tan IIA downregulated hypoxia-inducible factor-1α (HIF-1α) expression by blocking the AKT/mTOR signaling cascade.
- Tan IIA reduced the expression of glucose transporter 1 (GLUT1), pyruvate kinase M2 (PKM2), and hexokinase 2 (HK2), with CD147 silencing potentiating these effects.
Conclusions:
- Tan IIA disrupts the glycolytic pathway in prostate cancer cells.
- The mechanism involves suppression of the AKT/mTOR/HIF-1α axis and potential modulation of CD147.
- Tan IIA shows promise as an antitumor agent targeting prostate cancer's metabolic vulnerabilities.
