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Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer

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...

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Autores principales: Sikander, Mohammed, Malik, Shabnam, Chauhan, Neeraj, Khan, Parvez, Kumari, Sonam, Kashyap, Vivek Kumar, Khan, Sheema, Ganju, Aditya, Halaweish, Fathi T., Yallapu, Murali M., Jaggi, Meena, Chauhan, Subhash C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469021/
https://www.ncbi.nlm.nih.gov/pubmed/30875788
http://dx.doi.org/10.3390/cancers11030364
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author Sikander, Mohammed
Malik, Shabnam
Chauhan, Neeraj
Khan, Parvez
Kumari, Sonam
Kashyap, Vivek Kumar
Khan, Sheema
Ganju, Aditya
Halaweish, Fathi T.
Yallapu, Murali M.
Jaggi, Meena
Chauhan, Subhash C.
author_facet Sikander, Mohammed
Malik, Shabnam
Chauhan, Neeraj
Khan, Parvez
Kumari, Sonam
Kashyap, Vivek Kumar
Khan, Sheema
Ganju, Aditya
Halaweish, Fathi T.
Yallapu, Murali M.
Jaggi, Meena
Chauhan, Subhash C.
author_sort Sikander, Mohammed
collection PubMed
description 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.
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spelling pubmed-64690212019-04-23 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 M. Jaggi, Meena Chauhan, Subhash C. Cancers (Basel) Article 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. MDPI 2019-03-14 /pmc/articles/PMC6469021/ /pubmed/30875788 http://dx.doi.org/10.3390/cancers11030364 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sikander, Mohammed
Malik, Shabnam
Chauhan, Neeraj
Khan, Parvez
Kumari, Sonam
Kashyap, Vivek Kumar
Khan, Sheema
Ganju, Aditya
Halaweish, Fathi T.
Yallapu, Murali M.
Jaggi, Meena
Chauhan, Subhash C.
Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer
title Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer
title_full Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer
title_fullStr Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer
title_full_unstemmed Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer
title_short Cucurbitacin D Reprograms Glucose Metabolic Network in Prostate Cancer
title_sort cucurbitacin d reprograms glucose metabolic network in prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469021/
https://www.ncbi.nlm.nih.gov/pubmed/30875788
http://dx.doi.org/10.3390/cancers11030364
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