Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer

Area of Science:

• Oncology
• Metabolic pathways
• Cancer research

Background:

• Prostate cancer (PrCa) metastasis is a primary cause of cancer-related mortality.
• Metastatic PrCa cells exhibit altered glucose metabolism, presenting a therapeutic target.
• Reprogramming cancer cell metabolism offers a strategy to inhibit PrCa metastasis.

Purpose of the Study:

• To investigate the effect of cucurbitacin D (Cuc D) on glucose metabolism in metastatic PrCa cells.
• To explore Cuc D's potential as a therapeutic agent for inhibiting PrCa metastasis.

Main Methods:

• Assessed glucose uptake and lactate production in metastatic PrCa cells treated with Cuc D.
• Utilized molecular docking to predict Cuc D binding to GLUT1.
• Analyzed the expression of key oncogenic proteins and miR-132.
• Evaluated Cuc D's effect on PrCa cell tumorigenicity, metastasis, apoptosis, and cell cycle.
• Tested Cuc D efficacy in a PrCa xenograft mouse model.

Main Results:

• Cuc D significantly inhibited glucose uptake and lactate production in metastatic PrCa cells.
• Molecular docking indicated direct binding of Cuc D to GLUT1 (binding energy -8.5 kcal/mol).
• Cuc D treatment decreased GLUT1 expression and altered oncogenic protein and miR-132 levels.
• Cuc D reduced PrCa cell tumorigenicity and metastatic potential by inducing apoptosis and G2/M cell cycle arrest.
• In vivo studies showed Cuc D inhibited tumor growth, decreased GLUT1 and PCNA expression, and restored miR-132.

Conclusions:

• Cucurbitacin D effectively modulates glucose metabolism in prostate cancer.
• Cuc D demonstrates potential as a therapeutic agent for inhibiting PrCa metastasis by targeting GLUT1 and related pathways.