Cargando…

Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate

Malignant cells possess a unique metabolic machinery to endure unobstructed cell survival. It comprises several levels of metabolic networking consisting of 1) upregulated expression of membrane-associated transporter proteins, facilitating unhindered uptake of substrates; 2) upregulated metabolic p...

Descripción completa

Detalles Bibliográficos
Autores principales: Yadav, Saveg, Pandey, Shrish Kumar, Goel, Yugal, Temre, Mithlesh Kumar, Singh, Sukh Mahendra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620530/
https://www.ncbi.nlm.nih.gov/pubmed/31333455
http://dx.doi.org/10.3389/fphar.2019.00728
_version_ 1783434069228388352
author Yadav, Saveg
Pandey, Shrish Kumar
Goel, Yugal
Temre, Mithlesh Kumar
Singh, Sukh Mahendra
author_facet Yadav, Saveg
Pandey, Shrish Kumar
Goel, Yugal
Temre, Mithlesh Kumar
Singh, Sukh Mahendra
author_sort Yadav, Saveg
collection PubMed
description Malignant cells possess a unique metabolic machinery to endure unobstructed cell survival. It comprises several levels of metabolic networking consisting of 1) upregulated expression of membrane-associated transporter proteins, facilitating unhindered uptake of substrates; 2) upregulated metabolic pathways for efficient substrate utilization; 3) pH and redox homeostasis, conducive for driving metabolism; 4) tumor metabolism-dependent reconstitution of tumor growth promoting the external environment; 5) upregulated expression of receptors and signaling mediators; and 6) distinctive genetic and regulatory makeup to generate and sustain rearranged metabolism. This feat is achieved by a “battery of molecular patrons,” which acts in a highly cohesive and mutually coordinated manner to bestow immortality to neoplastic cells. Consequently, it is necessary to develop a multitargeted therapeutic approach to achieve a formidable inhibition of the diverse arrays of tumor metabolism. Among the emerging agents capable of such multifaceted targeting of tumor metabolism, an alkylating agent designated as 3-bromopyruvate (3-BP) has gained immense research focus because of its broad spectrum and specific antineoplastic action. Inhibitory effects of 3-BP are imparted on a variety of metabolic target molecules, including transporters, metabolic enzymes, and several other crucial stakeholders of tumor metabolism. Moreover, 3-BP ushers a reconstitution of the tumor microenvironment, a reversal of tumor acidosis, and recuperative action on vital organs and systems of the tumor-bearing host. Studies have been conducted to identify targets of 3-BP and its derivatives and characterization of target binding for further optimization. This review presents a brief and comprehensive discussion about the current state of knowledge concerning various aspects of tumor metabolism and explores the prospects of 3-BP as a safe and effective antineoplastic agent.
format Online
Article
Text
id pubmed-6620530
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-66205302019-07-22 Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate Yadav, Saveg Pandey, Shrish Kumar Goel, Yugal Temre, Mithlesh Kumar Singh, Sukh Mahendra Front Pharmacol Pharmacology Malignant cells possess a unique metabolic machinery to endure unobstructed cell survival. It comprises several levels of metabolic networking consisting of 1) upregulated expression of membrane-associated transporter proteins, facilitating unhindered uptake of substrates; 2) upregulated metabolic pathways for efficient substrate utilization; 3) pH and redox homeostasis, conducive for driving metabolism; 4) tumor metabolism-dependent reconstitution of tumor growth promoting the external environment; 5) upregulated expression of receptors and signaling mediators; and 6) distinctive genetic and regulatory makeup to generate and sustain rearranged metabolism. This feat is achieved by a “battery of molecular patrons,” which acts in a highly cohesive and mutually coordinated manner to bestow immortality to neoplastic cells. Consequently, it is necessary to develop a multitargeted therapeutic approach to achieve a formidable inhibition of the diverse arrays of tumor metabolism. Among the emerging agents capable of such multifaceted targeting of tumor metabolism, an alkylating agent designated as 3-bromopyruvate (3-BP) has gained immense research focus because of its broad spectrum and specific antineoplastic action. Inhibitory effects of 3-BP are imparted on a variety of metabolic target molecules, including transporters, metabolic enzymes, and several other crucial stakeholders of tumor metabolism. Moreover, 3-BP ushers a reconstitution of the tumor microenvironment, a reversal of tumor acidosis, and recuperative action on vital organs and systems of the tumor-bearing host. Studies have been conducted to identify targets of 3-BP and its derivatives and characterization of target binding for further optimization. This review presents a brief and comprehensive discussion about the current state of knowledge concerning various aspects of tumor metabolism and explores the prospects of 3-BP as a safe and effective antineoplastic agent. Frontiers Media S.A. 2019-07-04 /pmc/articles/PMC6620530/ /pubmed/31333455 http://dx.doi.org/10.3389/fphar.2019.00728 Text en Copyright © 2019 Yadav, Pandey, Goel, Temre and Singh http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yadav, Saveg
Pandey, Shrish Kumar
Goel, Yugal
Temre, Mithlesh Kumar
Singh, Sukh Mahendra
Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate
title Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate
title_full Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate
title_fullStr Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate
title_full_unstemmed Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate
title_short Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate
title_sort diverse stakeholders of tumor metabolism: an appraisal of the emerging approach of multifaceted metabolic targeting by 3-bromopyruvate
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620530/
https://www.ncbi.nlm.nih.gov/pubmed/31333455
http://dx.doi.org/10.3389/fphar.2019.00728
work_keys_str_mv AT yadavsaveg diversestakeholdersoftumormetabolismanappraisaloftheemergingapproachofmultifacetedmetabolictargetingby3bromopyruvate
AT pandeyshrishkumar diversestakeholdersoftumormetabolismanappraisaloftheemergingapproachofmultifacetedmetabolictargetingby3bromopyruvate
AT goelyugal diversestakeholdersoftumormetabolismanappraisaloftheemergingapproachofmultifacetedmetabolictargetingby3bromopyruvate
AT temremithleshkumar diversestakeholdersoftumormetabolismanappraisaloftheemergingapproachofmultifacetedmetabolictargetingby3bromopyruvate
AT singhsukhmahendra diversestakeholdersoftumormetabolismanappraisaloftheemergingapproachofmultifacetedmetabolictargetingby3bromopyruvate