Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer
Abstract
Prostate cancer (PrCa) metastasis is the major cause of mortality and morbidity among men. Metastatic PrCa cells are typically adopted for aberrant glucose metabolism. Thus, chemophores that reprogram altered glucose metabolic machinery in cancer cells can be useful agent for the repression of PrCa metastasis. Herein, we report that cucurbitacin D (Cuc D) effectively inhibits glucose uptake and lactate production in metastatic PrCa cells via modulating glucose metabolism. This metabolic shift by Cuc D was correlated with decreased expression of GLUT1 by its direct binding as suggested by its proficient molecular docking (binding energy −8.5 kcal/mol). Cuc D treatment also altered the expression of key oncogenic proteins and miR-132 that are known to be involved in glucose metabolism. Cuc D (0.1 to 1 µM) treatment inhibited tumorigenic and metastatic potential of human PrCa cells via inducing apoptosis and cell cycle arrest in G2/M phase. Cuc D treatment also showed inhibition of tumor growth in PrCa xenograft mouse model with concomitant decrease in the expression of GLUT1, PCNA and restoration of miR-132. These results suggest that Cuc D is a novel modulator of glucose metabolism and could be a promising therapeutic modality for the attenuation of PrCa metastasis.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 14, 2019
- Source ID
- 10.3390/cancers11030364
Entities
People
- Aditya Ganju
- Fathi Halaweish
- Meena Jaggi
- Mohammed Sikander
- Murali Yallapu
- Neeraj Chauhan
- Parvez Khan
- Shabnam Malik
- Sheema Khan
- Sonam Kumari
- Subhash Chauhan
- Vivek Kashyap
Organizations
- Foundation for the National Institutes of Health
- United States Department of Defense