A single chemotherapy administration induces muscle atrophy, mitochondrial alterations and apoptosis in breast cancer patients.
Anthracycline-cyclophosphamide
Mitochondria
Mitochondrial respiration
Muscle biopsies
Skeletal muscle deconditioning
Taxanes
Journal
Journal of cachexia, sarcopenia and muscle
ISSN: 2190-6009
Titre abrégé: J Cachexia Sarcopenia Muscle
Pays: Germany
ID NLM: 101552883
Informations de publication
Date de publication:
06 Jan 2024
06 Jan 2024
Historique:
revised:
13
11
2023
received:
08
08
2023
accepted:
20
11
2023
medline:
7
1
2024
pubmed:
7
1
2024
entrez:
6
1
2024
Statut:
aheadofprint
Résumé
Breast cancer patients are commonly treated with sequential administrations of epirubicin-cyclophosphamide (EC) and paclitaxel (TAX). The chronic effect of this treatment induces skeletal muscle alterations, but the specific effect of each chemotherapy agent is unknown. This study aimed to investigate the effect of EC or TAX administration on skeletal muscle homeostasis in breast cancer patients. Twenty early breast cancer patients undergoing EC followed by TAX chemotherapies were included. Two groups of 10 women were established and performed vastus lateralis skeletal muscle biopsies either before the first administration (pre) of EC (50 ± 14 years) or TAX (50 ± 16 years) and 4 days later (post). Mitochondrial respiratory capacity recording, reactive oxygen species production, western blotting and histological analyses were performed. Decrease in muscle fibres cross-sectional area was only observed post-EC (-25%; P < 0.001), associated with a reduction in mitochondrial respiratory capacity for the complex I (CI)-linked substrate state (-32%; P = 0.001), oxidative phosphorylation (OXPHOS) by CI (-35%; P = 0.002), CI&CII (-26%; P = 0.022) and CII (-24%; P = 0.027). If H We demonstrated that a single administration of EC induced, in only 4 days, skeletal muscle atrophy and mitochondrial alterations in breast cancer patients. These alterations were characterized by reductions in mitochondrial function and content as well as impairment of mitochondrial dynamics and an increase in apoptosis. TAX administration did not worsen these alterations as this group had already received EC during the preceding weeks. However, it resulted in an increased apoptosis, likely in response to the increased H
Sections du résumé
BACKGROUND
BACKGROUND
Breast cancer patients are commonly treated with sequential administrations of epirubicin-cyclophosphamide (EC) and paclitaxel (TAX). The chronic effect of this treatment induces skeletal muscle alterations, but the specific effect of each chemotherapy agent is unknown. This study aimed to investigate the effect of EC or TAX administration on skeletal muscle homeostasis in breast cancer patients.
METHODS
METHODS
Twenty early breast cancer patients undergoing EC followed by TAX chemotherapies were included. Two groups of 10 women were established and performed vastus lateralis skeletal muscle biopsies either before the first administration (pre) of EC (50 ± 14 years) or TAX (50 ± 16 years) and 4 days later (post). Mitochondrial respiratory capacity recording, reactive oxygen species production, western blotting and histological analyses were performed.
RESULTS
RESULTS
Decrease in muscle fibres cross-sectional area was only observed post-EC (-25%; P < 0.001), associated with a reduction in mitochondrial respiratory capacity for the complex I (CI)-linked substrate state (-32%; P = 0.001), oxidative phosphorylation (OXPHOS) by CI (-35%; P = 0.002), CI&CII (-26%; P = 0.022) and CII (-24%; P = 0.027). If H
CONCLUSIONS
CONCLUSIONS
We demonstrated that a single administration of EC induced, in only 4 days, skeletal muscle atrophy and mitochondrial alterations in breast cancer patients. These alterations were characterized by reductions in mitochondrial function and content as well as impairment of mitochondrial dynamics and an increase in apoptosis. TAX administration did not worsen these alterations as this group had already received EC during the preceding weeks. However, it resulted in an increased apoptosis, likely in response to the increased H
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Institut de Cancérologie Strasbourg Europe (ICANS)
Organisme : Investments in the Future programme of the French government (IdEx Unistra)
Organisme : OCOVAS
Informations de copyright
© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.
Références
Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet Lond Engl 2018;391:1023-1075.
Mallard J, Hucteau E, Hureau TJ, Pagano AF. Skeletal muscle deconditioning in breast cancer patients undergoing chemotherapy: current knowledge and insights from other cancers. Front Cell Dev Biol 2021;9:2550.
Guigni BA, Callahan DM, Tourville TW, Miller MS, Fiske B, Voigt T, et al. Skeletal muscle atrophy and dysfunction in breast cancer patients: role for chemotherapy-derived oxidant stress. Am J Physiol Cell Physiol 2018;315:C744-C756.
Mijwel S, Cardinale DA, Norrbom J, Chapman M, Ivarsson N, Wengström Y, et al. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer. FASEB J 2018;32:fj.201700968R.
Peel AB, Thomas SM, Dittus K, Jones LW, Lakoski SG. Cardiorespiratory fitness in breast cancer patients: a call for normative values. J Am Heart Assoc 2014;3:e000432.
Hiensch AE, Bolam KA, Mijwel S, Jeneson JAL, Huitema ADR, Kranenburg O, et al. Doxorubicin-induced skeletal muscle atrophy: elucidating the underlying molecular pathways. Acta Physiol (Oxf) 2019;229:e13400.
Gilliam LAA, Fisher-Wellman KH, Lin C-T, Maples JM, Cathey BL, Neufer PD. The anticancer agent doxorubicin disrupts mitochondrial energy metabolism and redox balance in skeletal muscle. Free Radic Biol Med 2013;65:988-996.
Gilliam LAA, Lark DS, Reese LR, Torres MJ, Ryan TE, Lin C-T, et al. Targeted overexpression of mitochondrial catalase protects against cancer chemotherapy-induced skeletal muscle dysfunction. Am J Physiol Endocrinol Metab 2016;311:E293-E301.
Min K, Kwon O-S, Smuder AJ, Wiggs MP, Sollanek KJ, Christou DD, et al. Increased mitochondrial emission of reactive oxygen species and calpain activation are required for doxorubicin-induced cardiac and skeletal muscle myopathy. J Physiol 2015;593:2017-2036.
Smuder AJ, Kavazis AN, Min K, Powers SK. Exercise protects against doxorubicin-induced oxidative stress and proteolysis in skeletal muscle. J Appl Physiol Bethesda Md 1985;2011:935-942.
Yu AP, Pei XM, Sin TK, Yip SP, Yung BY, Chan LW, et al. Acylated and unacylated ghrelin inhibit doxorubicin-induced apoptosis in skeletal muscle. Acta Physiol (Oxf) 2014;211:201-213.
Crouch M-L, Knowels G, Stuppard R, Ericson NG, Bielas JH, Marcinek DJ, et al. Cyclophosphamide leads to persistent deficits in physical performance and in vivo mitochondria function in a mouse model of chemotherapy late effects. PLoS ONE 2017;12:e0181086.
Torres MJ, Zhang X, Slentz DH, Koves TR, Patel H, Truskey GA, et al. Chemotherapeutic drug screening in 3D-bioengineered human myobundles provides insight into taxane-induced myotoxicities. iScience 2022;25:105189.
Mallard J, Hucteau E, Charles A-L, Bender L, Baeza C, Pélissie M, et al. Chemotherapy impairs skeletal muscle mitochondrial homeostasis in early breast cancer patients. J Cachexia Sarcopenia Muscle 2022;13:1896-1907.
Murach KA, Dungan CM, Kosmac K, Voigt TB, Tourville TW, Miller MS, et al. Fiber typing human skeletal muscle with fluorescent immunohistochemistry. J Appl Physiol Bethesda Md 1985;2019:1632-1639.
Guilhot C, Fovet T, Delobel P, Dargegen M, Jasmin BJ, Brioche T, et al. Severe muscle deconditioning triggers early extracellular matrix remodeling and resident stem cell differentiation into adipocytes in healthy men. Int J Mol Sci 2022;23:5489.
Lexell J, Taylor CC, Sjöström M. What is the cause of the ageing atrophy? Total number, size and proportion of different fiber types studied in whole vastus lateralis muscle from 15- to 83-year-old men. J Neurol Sci 1988;84:275-294.
Chan MC, Arany Z. The many roles of PGC-1α in muscle - recent developments. Metabolism 2014;63:441-451.
Weibel ER, Bacigalupe LD, Schmitt B, Hoppeler H. Allometric scaling of maximal metabolic rate in mammals: muscle aerobic capacity as determinant factor. Respir Physiol Neurobiol 2004;140:115-132.
Mallard J, Hucteau E, Schott R, Trensz P, Pflumio C, Kalish-Weindling M, et al. Early skeletal muscle deconditioning and reduced exercise capacity during (neo)adjuvant chemotherapy in patients with breast cancer. Cancer 2023;129:215-225.
Pernas L, Scorrano L. Mito-morphosis: mitochondrial fusion, fission, and cristae remodeling as key mediators of cellular function. Annu Rev Physiol 2016;78:505-531.
Brown JL, Rosa-Caldwell ME, Lee DE, Blackwell TA, Brown LA, Perry RA, et al. Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice. J Cachexia Sarcopenia Muscle 2017;8:926-938.
Barreto R, Waning DL, Gao H, Liu Y, Zimmers TA, Bonetto A. Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs. Oncotarget 2016;7:43442-43460.
Pradeepkiran JA, Reddy PH. Defective mitophagy in Alzheimer's disease. Ageing Res Rev 2020;64:101191.
Hyatt H, Deminice R, Yoshihara T, Powers SK. Mitochondrial dysfunction induces muscle atrophy during prolonged inactivity: a review of the causes and effects. Arch Biochem Biophys 2019;662:49-60.
Xiang J, Wan C, Guo R, Guo D. Is hydrogen peroxide a suitable apoptosis inducer for all cell types? Biomed Res Int 2016;2016:7343965.
Viola HM, Arthur PG, Hool LC. Transient exposure to hydrogen peroxide causes an increase in mitochondria-derived superoxide as a result of sustained alteration in L-type Ca2+ channel function in the absence of apoptosis in ventricular myocytes. Circ Res 2007;100:1036-1044.
Lin H-Y, Shen S-C, Lin C-W, Yang L-Y, Chen Y-C. Baicalein inhibition of hydrogen peroxide-induced apoptosis via ROS-dependent heme oxygenase 1 gene expression. Biochim Biophys Acta 2007;1773:1073-1086.
Singh M, Sharma H, Singh N. Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway. Mitochondrion 2007;7:367-373.
Baechler BL, Bloemberg D, Quadrilatero J. Mitophagy regulates mitochondrial network signaling, oxidative stress, and apoptosis during myoblast differentiation. Autophagy 2019;15:1606-1619.
Chacon-Cabrera A, Fermoselle C, Urtreger AJ, Mateu-Jimenez M, Diament MJ, de Kier Joffé EDB, et al. Pharmacological strategies in lung cancer-induced cachexia: effects on muscle proteolysis, autophagy, structure, and weakness. J Cell Physiol 2014;229:1660-1672.
Salazar-Degracia A, Blanco D, Vilà-Ubach M, de Biurrun G, de Solórzano CO, Montuenga LM, et al. Phenotypic and metabolic features of mouse diaphragm and gastrocnemius muscles in chronic lung carcinogenesis: influence of underlying emphysema. J Transl Med 2016;14:244.
Schwartz LM. Skeletal muscles do not undergo apoptosis during either atrophy or programmed cell death-revisiting the myonuclear domain hypothesis. Front Physiol 2018;9:1887.
Gram M, Dahl R, Dela F. Physical inactivity and muscle oxidative capacity in humans. Eur J Sport Sci 2014;14:376-383.
Horber FF, Hoppeler H, Herren D, Claassen H, Howald H, Gerber C, et al. Altered skeletal muscle ultrastructure in renal transplant patients on prednisone. Kidney Int 1986;30:411-416.
Krivickas LS, Dorer DJ, Ochala J, Frontera WR. Relationship between force and size in human single muscle fibres. Exp Physiol 2011;96:539-547.
da Costa R, Passos GF, Quintão NLM, Fernandes ES, Maia JRLCB, Campos MM, et al. Taxane-induced neurotoxicity: Pathophysiology and therapeutic perspectives. Br J Pharmacol 2020;177:3127-3146.
Nicolazzi MA, Carnicelli A, Fuorlo M, Scaldaferri A, Masetti R, Landolfi R, et al. Anthracycline and trastuzumab-induced cardiotoxicity in breast cancer. Eur Rev Med Pharmacol Sci 2018;22:2175-2185.
Hucteau E, Mallard J, Pivot X, Schott R, Pflumio C, Trensz P, et al. Exacerbated central fatigue and reduced exercise capacity in early-stage breast cancer patients treated with chemotherapy. Eur J Appl Physiol 2023;123:1567-1581.
von Haehling S, Coats AJS, Anker SD. Ethical guidelines for publishing in the Journal of Cachexia, Sarcopenia and Muscle: update 2021. J Cachexia Sarcopenia Muscle 2021;12:2259-2261.