Gorini, S; De Angelis, A; Berrino, L; Malara, N; Rosano, G; Ferraro, E
(2018)
Chemotherapeutic Drugs and Mitochondrial Dysfunction: Focus on Doxorubicin, Trastuzumab, and Sunitinib.
Oxid Med Cell Longev, 2018.
p. 7582730.
ISSN 1942-0994
https://doi.org/10.1155/2018/7582730
SGUL Authors: Rosano, Giuseppe Massimo Claudio
Abstract
Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic-induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible. Vice versa, doxorubicin-induced toxicity not only includes mitochondria damage but can also lead to a more robust and extensive cell injury which is often irreversible and lethal. Drugs interfering with mitochondrial functionality determine the depletion of ATP reservoirs and lead to subsequent reversible contractile dysfunction. Mitochondrial damage includes the impairment of the respiratory chain and the loss of mitochondrial membrane potential with subsequent disruption of cellular energetic. In a context of increased stress, AMPK has a key role in maintaining energy homeostasis, and inhibition of the AMPK pathway is one of the proposed mechanisms possibly mediating mitochondrial toxicity due to chemotherapeutics. Therapies targeting and protecting cell metabolism and energy management might be useful tools in protecting muscular tissues against the toxicity induced by chemotherapeutic drugs.
Item Type: |
Article
|
Additional Information: |
Copyright © 2018 Stefania Gorini et al. This is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corrigendum available at http://dx.doi.org/10.1155/2019/9601435 |
Keywords: |
Doxorubicin, Humans, Indoles, Mitochondria, Heart, Pyrroles, Sunitinib, Trastuzumab, Mitochondria, Heart, Humans, Pyrroles, Indoles, Doxorubicin, Trastuzumab, Sunitinib |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
Oxid Med Cell Longev |
ISSN: |
1942-0994 |
Language: |
eng |
Dates: |
Date | Event |
---|
18 March 2018 | Published | 6 February 2018 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
Project ID | Funder | Funder ID |
---|
RF2010-2318508 | Italian Ministry of Health for Institutional Research | UNSPECIFIED | PON03PE_00078_2 | UNSPECIFIED | UNSPECIFIED |
|
PubMed ID: |
29743983 |
Web of Science ID: |
WOS:000428919800001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/111195 |
Publisher's version: |
https://doi.org/10.1155/2018/7582730 |
Statistics
Item downloaded times since 19 Sep 2019.
Actions (login required)
![Edit Item](/style/images/action_view.png) |
Edit Item |