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Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer
- 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.
- Subjects :
- Cancer Research
Cell cycle checkpoint
cucurbitacin D
Glucose uptake
urologic and male genital diseases
lcsh:RC254-282
Article
PrCa
miRNAs and glucose metabolism
Metastasis
03 medical and health sciences
Prostate cancer
0302 clinical medicine
medicine
Cucurbitacin D
030304 developmental biology
0303 health sciences
biology
Chemistry
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
Oncology
Apoptosis
030220 oncology & carcinogenesis
Cancer cell
Cancer research
biology.protein
GLUT1
Subjects
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