Back to Search Start Over

Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer

Authors :
Murali M. Yallapu
Meena Jaggi
Aditya Ganju
Vivek K. Kashyap
Neeraj Chauhan
Subhash C. Chauhan
Mohammed Sikander
Parvez Khan
Sheema Khan
Sonam Kumari
Fathi T. Halaweish
Shabnam Malik
Source :
Cancers; Volume 11; Issue 3; Pages: 364, Cancers, Vol 11, Iss 3, p 364 (2019), Cancers
Publication Year :
2019
Publisher :
Multidisciplinary Digital Publishing Institute, 2019.

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.

Details

Language :
English
ISSN :
20726694
Database :
OpenAIRE
Journal :
Cancers; Volume 11; Issue 3; Pages: 364
Accession number :
edsair.doi.dedup.....1d5bd86bfda7280094782c55a40e6c2e
Full Text :
https://doi.org/10.3390/cancers11030364