Cucurbitacin D reprograms glucose metabolic network in prostate cancer

Mohammed Sikander, Shabnam Malik, Neeraj Chauhan, Parvez Khan, Sonam Kumari, Vivek Kumar Kashyap, Sheema Khan, Aditya Ganju, Fathi T. Halaweish, Murali Yallapu, Meena Jaggi, Subhash Chauhan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number364
JournalCancers
Volume11
Issue number3
DOIs
StatePublished - Mar 1 2019

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Metabolic Networks and Pathways
Prostatic Neoplasms
Glucose
Neoplasm Metastasis
G2 Phase
Proliferating Cell Nuclear Antigen
Therapeutics
Cell Cycle Checkpoints
cucurbitacin D
Heterografts
Cell Division
Lactic Acid
Neoplasms
Apoptosis
Morbidity
Mortality
Growth
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Sikander, M., Malik, S., Chauhan, N., Khan, P., Kumari, S., Kashyap, V. K., ... Chauhan, S. (2019). Cucurbitacin D reprograms glucose metabolic network in prostate cancer. Cancers, 11(3), [364]. https://doi.org/10.3390/cancers11030364

Cucurbitacin D reprograms glucose metabolic network in prostate cancer. / Sikander, Mohammed; Malik, Shabnam; Chauhan, Neeraj; Khan, Parvez; Kumari, Sonam; Kashyap, Vivek Kumar; Khan, Sheema; Ganju, Aditya; Halaweish, Fathi T.; Yallapu, Murali; Jaggi, Meena; Chauhan, Subhash.

In: Cancers, Vol. 11, No. 3, 364, 01.03.2019.

Research output: Contribution to journalArticle

Sikander, M, Malik, S, Chauhan, N, Khan, P, Kumari, S, Kashyap, VK, Khan, S, Ganju, A, Halaweish, FT, Yallapu, M, Jaggi, M & Chauhan, S 2019, 'Cucurbitacin D reprograms glucose metabolic network in prostate cancer', Cancers, vol. 11, no. 3, 364. https://doi.org/10.3390/cancers11030364
Sikander M, Malik S, Chauhan N, Khan P, Kumari S, Kashyap VK et al. Cucurbitacin D reprograms glucose metabolic network in prostate cancer. Cancers. 2019 Mar 1;11(3). 364. https://doi.org/10.3390/cancers11030364
Sikander, Mohammed ; Malik, Shabnam ; Chauhan, Neeraj ; Khan, Parvez ; Kumari, Sonam ; Kashyap, Vivek Kumar ; Khan, Sheema ; Ganju, Aditya ; Halaweish, Fathi T. ; Yallapu, Murali ; Jaggi, Meena ; Chauhan, Subhash. / Cucurbitacin D reprograms glucose metabolic network in prostate cancer. In: Cancers. 2019 ; Vol. 11, No. 3.
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