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Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state
BACKGROUND: Obesity is associated with increased risk, poor prognosis and outcome of therapy, in various cancers. Obesity-associated factors or adipokines, especially leptin and resistin, are purported to promote growth, survival, proliferation, and invasiveness of cancer cells. However, the mechani...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859707/ https://www.ncbi.nlm.nih.gov/pubmed/29568521 http://dx.doi.org/10.1186/s40170-018-0176-5 |
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author | Malvi, Parmanand Chaube, Balkrishna Singh, Shivendra Vikram Mohammad, Naoshad Vijayakumar, Maleppillil Vavachan Singh, Snahlata Chouhan, Surbhi Bhat, Manoj Kumar |
author_facet | Malvi, Parmanand Chaube, Balkrishna Singh, Shivendra Vikram Mohammad, Naoshad Vijayakumar, Maleppillil Vavachan Singh, Snahlata Chouhan, Surbhi Bhat, Manoj Kumar |
author_sort | Malvi, Parmanand |
collection | PubMed |
description | BACKGROUND: Obesity is associated with increased risk, poor prognosis and outcome of therapy, in various cancers. Obesity-associated factors or adipokines, especially leptin and resistin, are purported to promote growth, survival, proliferation, and invasiveness of cancer cells. However, the mechanistic link between these adipokines and therapeutic response in malignancies is not clearly understood. METHODS: ob/ob and db/db mouse models were used in this study to evaluate the role of leptin and resistin towards the outcome of dacarbazine (DTIC) therapy in melanoma. Unique in vitro approaches were employed to complement in vivo findings by culturing melanoma cells in the serum collected from the experimental mice. RESULTS: Here, we have shown the role of important adipokines leptin and resistin in growth and the outcome of DTIC therapy in melanoma. Both leptin and resistin not only enhance proliferation of melanoma cells but also are involved in impairing the therapeutic efficacy of DTIC. Leptin and resistin treatment caused an increase in the protein levels of fatty acid synthase (FASN) and caveolin 1 (Cav-1) respectively, through their stabilization in A375 cells. Further, it was observed that leptin and resistin impaired the response of melanoma cells to DTIC via upregulation of heat shock protein 90 (Hsp90) and P-glycoprotein (P-gp) respectively. CONCLUSION: These findings unraveled the involvement of adipokines (leptin and resistin) in melanoma progression, and more importantly, in the outcome of DTIC therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40170-018-0176-5) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5859707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58597072018-03-22 Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state Malvi, Parmanand Chaube, Balkrishna Singh, Shivendra Vikram Mohammad, Naoshad Vijayakumar, Maleppillil Vavachan Singh, Snahlata Chouhan, Surbhi Bhat, Manoj Kumar Cancer Metab Rapid Communication BACKGROUND: Obesity is associated with increased risk, poor prognosis and outcome of therapy, in various cancers. Obesity-associated factors or adipokines, especially leptin and resistin, are purported to promote growth, survival, proliferation, and invasiveness of cancer cells. However, the mechanistic link between these adipokines and therapeutic response in malignancies is not clearly understood. METHODS: ob/ob and db/db mouse models were used in this study to evaluate the role of leptin and resistin towards the outcome of dacarbazine (DTIC) therapy in melanoma. Unique in vitro approaches were employed to complement in vivo findings by culturing melanoma cells in the serum collected from the experimental mice. RESULTS: Here, we have shown the role of important adipokines leptin and resistin in growth and the outcome of DTIC therapy in melanoma. Both leptin and resistin not only enhance proliferation of melanoma cells but also are involved in impairing the therapeutic efficacy of DTIC. Leptin and resistin treatment caused an increase in the protein levels of fatty acid synthase (FASN) and caveolin 1 (Cav-1) respectively, through their stabilization in A375 cells. Further, it was observed that leptin and resistin impaired the response of melanoma cells to DTIC via upregulation of heat shock protein 90 (Hsp90) and P-glycoprotein (P-gp) respectively. CONCLUSION: These findings unraveled the involvement of adipokines (leptin and resistin) in melanoma progression, and more importantly, in the outcome of DTIC therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40170-018-0176-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-20 /pmc/articles/PMC5859707/ /pubmed/29568521 http://dx.doi.org/10.1186/s40170-018-0176-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Rapid Communication Malvi, Parmanand Chaube, Balkrishna Singh, Shivendra Vikram Mohammad, Naoshad Vijayakumar, Maleppillil Vavachan Singh, Snahlata Chouhan, Surbhi Bhat, Manoj Kumar Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state |
title | Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state |
title_full | Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state |
title_fullStr | Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state |
title_full_unstemmed | Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state |
title_short | Elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state |
title_sort | elevated circulatory levels of leptin and resistin impair therapeutic efficacy of dacarbazine in melanoma under obese state |
topic | Rapid Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859707/ https://www.ncbi.nlm.nih.gov/pubmed/29568521 http://dx.doi.org/10.1186/s40170-018-0176-5 |
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