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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6469021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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