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Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma
Multiple myeloma (MM) remains an incurable tumor due to the high rate of relapse that still occurs. Acquired drug resistance represents the most challenging obstacle to the extension of survival and several studies have been conducted to understand the mechanisms of this phenomenon. Mitochondrial pa...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922387/ https://www.ncbi.nlm.nih.gov/pubmed/33669515 http://dx.doi.org/10.3390/cells10020439 |
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author | Innao, Vanessa Rizzo, Vincenzo Allegra, Andrea Gaetano Musolino, Caterina Allegra, Alessandro |
author_facet | Innao, Vanessa Rizzo, Vincenzo Allegra, Andrea Gaetano Musolino, Caterina Allegra, Alessandro |
author_sort | Innao, Vanessa |
collection | PubMed |
description | Multiple myeloma (MM) remains an incurable tumor due to the high rate of relapse that still occurs. Acquired drug resistance represents the most challenging obstacle to the extension of survival and several studies have been conducted to understand the mechanisms of this phenomenon. Mitochondrial pathways have been extensively investigated, demonstrating that cancer cells become resistant to drugs by reprogramming their metabolic assessment. MM cells acquire resistance to proteasome inhibitors (PIs), activating protection programs, such as a reduction in oxidative stress, down-regulating pro-apoptotic, and up-regulating anti-apoptotic signals. Knowledge of the mechanisms through which tumor cells escape control of the immune system and acquire resistance to drugs has led to the creation of new compounds that can restore the response by leading to cell death. In this scenario, based on all literature data available, our review represents the first collection of anti-mitochondrial compounds able to overcome drug resistance in MM. Caspase-independent mechanisms, mainly based on increased oxidative stress, result from 2-methoxyestradiol, Artesunate, ascorbic acid, Dihydroartemisinin, Evodiamine, b-AP15, VLX1570, Erw-ASNase, and TAK-242. Other agents restore PIs’ efficacy through caspase-dependent tools, such as CDDO-Im, NOXA-inhibitors, FTY720, GCS-100, LBH589, a derivative of ellipticine, AT-101, KD5170, SMAC-mimetics, glutaminase-1 (GLS1)-inhibitors, and thenoyltrifluoroacetone. Each of these substances improved the efficacy rates when employed in combination with the most frequently used antimyeloma drugs. |
format | Online Article Text |
id | pubmed-7922387 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79223872021-03-03 Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma Innao, Vanessa Rizzo, Vincenzo Allegra, Andrea Gaetano Musolino, Caterina Allegra, Alessandro Cells Review Multiple myeloma (MM) remains an incurable tumor due to the high rate of relapse that still occurs. Acquired drug resistance represents the most challenging obstacle to the extension of survival and several studies have been conducted to understand the mechanisms of this phenomenon. Mitochondrial pathways have been extensively investigated, demonstrating that cancer cells become resistant to drugs by reprogramming their metabolic assessment. MM cells acquire resistance to proteasome inhibitors (PIs), activating protection programs, such as a reduction in oxidative stress, down-regulating pro-apoptotic, and up-regulating anti-apoptotic signals. Knowledge of the mechanisms through which tumor cells escape control of the immune system and acquire resistance to drugs has led to the creation of new compounds that can restore the response by leading to cell death. In this scenario, based on all literature data available, our review represents the first collection of anti-mitochondrial compounds able to overcome drug resistance in MM. Caspase-independent mechanisms, mainly based on increased oxidative stress, result from 2-methoxyestradiol, Artesunate, ascorbic acid, Dihydroartemisinin, Evodiamine, b-AP15, VLX1570, Erw-ASNase, and TAK-242. Other agents restore PIs’ efficacy through caspase-dependent tools, such as CDDO-Im, NOXA-inhibitors, FTY720, GCS-100, LBH589, a derivative of ellipticine, AT-101, KD5170, SMAC-mimetics, glutaminase-1 (GLS1)-inhibitors, and thenoyltrifluoroacetone. Each of these substances improved the efficacy rates when employed in combination with the most frequently used antimyeloma drugs. MDPI 2021-02-19 /pmc/articles/PMC7922387/ /pubmed/33669515 http://dx.doi.org/10.3390/cells10020439 Text en © 2021 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 | Review Innao, Vanessa Rizzo, Vincenzo Allegra, Andrea Gaetano Musolino, Caterina Allegra, Alessandro Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma |
title | Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma |
title_full | Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma |
title_fullStr | Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma |
title_full_unstemmed | Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma |
title_short | Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma |
title_sort | promising anti-mitochondrial agents for overcoming acquired drug resistance in multiple myeloma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922387/ https://www.ncbi.nlm.nih.gov/pubmed/33669515 http://dx.doi.org/10.3390/cells10020439 |
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