Compound Z526 alleviates chemotherapy-induced cachectic muscle loss by ameliorating oxidative stress-driven protein metabolic imbalance and apoptosis
Copyright © 2024. Published by Elsevier B.V..
Chemotherapy is one of the primary and indispensable intervention against cancers though it is always accompanied by severe side effects especially cachexia. Cachexia is a fatal metabolic disorder syndrome, mainly characterized by muscle loss. Oxidative stress is the key factor that trigger cachectic muscle loss by inducing imbalance in protein metabolism and apoptosis. Here, we showed an oral compound (Z526) exhibited potent alleviating effects on C2C12 myotube atrophy induced by various chemotherapeutic agents in vitro as well as mice muscle loss and impaired grip force induced by oxaliplatin in vivo. Furthermore, Z526 also could ameliorate C2C12 myotube atrophy induced by the combination of chemotherapeutic agents with conditioned medium of various tumor cells in vitro as well as mice muscle atrophy of C26 tumor-bearing mice treated with oxaliplatin. The pharmacological effects of Z526 were based on its potency in reducing oxidative stress in cachectic myocytes and muscle tissues, which inhibited the activation of NF-κB and STAT3 to decrease Atrogin-1-mediated protein degradation, activated the AKT/mTOR signaling pathway to promote protein synthesis, regulated Bcl-2/BAX ratio to reduce Caspase-3-triggered apoptosis. Our work suggested Z526 to be an optional strategy for ameliorating cachexia muscle atrophy in the multimodality treatment of cancers.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
European journal of pharmacology - (2024) vom: 27. März, Seite 176538 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gu, Xiaofan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Apoptosis |
|---|
| Anmerkungen: |
Date Revised 29.03.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1016/j.ejphar.2024.176538 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370424646 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370424646 | ||
| 003 | DE-627 | ||
| 005 | 20240331002514.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240331s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejphar.2024.176538 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1357.xml |
| 035 | |a (DE-627)NLM370424646 | ||
| 035 | |a (NLM)38552940 | ||
| 035 | |a (PII)S0014-2999(24)00226-7 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gu, Xiaofan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Compound Z526 alleviates chemotherapy-induced cachectic muscle loss by ameliorating oxidative stress-driven protein metabolic imbalance and apoptosis |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a Chemotherapy is one of the primary and indispensable intervention against cancers though it is always accompanied by severe side effects especially cachexia. Cachexia is a fatal metabolic disorder syndrome, mainly characterized by muscle loss. Oxidative stress is the key factor that trigger cachectic muscle loss by inducing imbalance in protein metabolism and apoptosis. Here, we showed an oral compound (Z526) exhibited potent alleviating effects on C2C12 myotube atrophy induced by various chemotherapeutic agents in vitro as well as mice muscle loss and impaired grip force induced by oxaliplatin in vivo. Furthermore, Z526 also could ameliorate C2C12 myotube atrophy induced by the combination of chemotherapeutic agents with conditioned medium of various tumor cells in vitro as well as mice muscle atrophy of C26 tumor-bearing mice treated with oxaliplatin. The pharmacological effects of Z526 were based on its potency in reducing oxidative stress in cachectic myocytes and muscle tissues, which inhibited the activation of NF-κB and STAT3 to decrease Atrogin-1-mediated protein degradation, activated the AKT/mTOR signaling pathway to promote protein synthesis, regulated Bcl-2/BAX ratio to reduce Caspase-3-triggered apoptosis. Our work suggested Z526 to be an optional strategy for ameliorating cachexia muscle atrophy in the multimodality treatment of cancers | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Cachectic muscle loss | |
| 650 | 4 | |a Chemotherapeutic agents | |
| 650 | 4 | |a Oxidative stress | |
| 650 | 4 | |a Protein metabolic imbalance | |
| 650 | 4 | |a Z526 | |
| 700 | 1 | |a Lu, Shanshan |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Shuang |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Guangyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Weili |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xuan |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Xiaochun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiongwen |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of pharmacology |d 1967 |g (2024) vom: 27. März, Seite 176538 |w (DE-627)NLM000029769 |x 1879-0712 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:27 |g month:03 |g pages:176538 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejphar.2024.176538 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 27 |c 03 |h 176538 | ||