Arsenic trioxide-induced apoptosis in H9c2 cardiomyocytes: implications in cardiotoxicity
- PMID: 18346055
- DOI: 10.1111/j.1742-7843.2007.00150.x
Arsenic trioxide-induced apoptosis in H9c2 cardiomyocytes: implications in cardiotoxicity
Abstract
Arsenic trioxide (As(2)O(3)) achieved dramatic remissions in patients with acute promyelocytic leukaemia. Clinical reports have shown that treatment was associated with cardiotoxicity. We investigated the toxic mechanisms of As(2)O(3) in H9c2 cardiomyocytes. Clinically relevant concentrations of As(2)O(3) (2-10 microM) reduced the viability of H9c2 cells in a concentration-dependent manner. The decreased cell viability was because As(2)O(3) induced cell apoptosis (cell shrinkage, nuclear alterations and caspase-3 activation), or even necrosis at higher concentrations. Inhibition of caspase-3 with a specific inhibitor, Ac-DEVD-CHO, suppressed apoptosis induced by As(2)O(3). In addition, reactive oxygen species formation and cellular Ca(2+) overload were observed in H9c2 cells exposed to As(2)O(3), which was partly inhibited by vitamin E and verapamil. These results suggest that As(2)O(3)-induced cardiotoxicity is mediated, at least in part, by activation of caspase-3 pathway, which may be triggered by reactive oxygen species formation and intracellular Ca(2+) overload.
Similar articles
-
Metallothionein prevention of arsenic trioxide-induced cardiac cell death is associated with its inhibition of mitogen-activated protein kinases activation in vitro and in vivo.Toxicol Lett. 2013 Jul 18;220(3):277-85. doi: 10.1016/j.toxlet.2013.04.025. Epub 2013 May 9. Toxicol Lett. 2013. PMID: 23664956
-
Protective effect of calceolarioside on adriamycin-induced cardiomyocyte toxicity.Eur J Pharmacol. 2006 Jul 10;541(1-2):24-32. doi: 10.1016/j.ejphar.2006.04.045. Epub 2006 May 9. Eur J Pharmacol. 2006. PMID: 16780832
-
JWA is required for arsenic trioxide induced apoptosis in HeLa and MCF-7 cells via reactive oxygen species and mitochondria linked signal pathway.Toxicol Appl Pharmacol. 2008 Jul 1;230(1):33-40. doi: 10.1016/j.taap.2008.01.041. Epub 2008 Feb 20. Toxicol Appl Pharmacol. 2008. PMID: 18387645
-
[Arsenic trioxide: "a successful poison" in patients with acute promyelocytic leukemia].Dtsch Med Wochenschr. 2007 Feb 16;132(7):330-6. doi: 10.1055/s-2007-959329. Dtsch Med Wochenschr. 2007. PMID: 17286223 Review. German. No abstract available.
-
An Overview on Arsenic Trioxide-Induced Cardiotoxicity.Cardiovasc Toxicol. 2019 Apr;19(2):105-119. doi: 10.1007/s12012-018-09504-7. Cardiovasc Toxicol. 2019. PMID: 30617460 Review.
Cited by
-
Arsenic trioxide: applications, mechanisms of action, toxicity and rescue strategies to date.Arch Pharm Res. 2024 Mar;47(3):249-271. doi: 10.1007/s12272-023-01481-y. Epub 2023 Dec 26. Arch Pharm Res. 2024. PMID: 38147202 Review.
-
An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications.Cell Death Discov. 2023 Jul 27;9(1):266. doi: 10.1038/s41420-023-01558-z. Cell Death Discov. 2023. PMID: 37500645 Free PMC article. Review.
-
The involvement and therapeutic potential of lncRNA Kcnq1ot1/miR-34a-5p/Sirt1 pathway in arsenic trioxide-induced cardiotoxicity.J Transl Med. 2023 Jan 28;21(1):52. doi: 10.1186/s12967-023-03895-0. J Transl Med. 2023. PMID: 36707890 Free PMC article.
-
Potential Protective Effect of Spirulina Platensis on Sodium Arsenite Induced Cardiotoxicity in Male Rats.Tissue Barriers. 2022 Apr 3;10(2):1983330. doi: 10.1080/21688370.2021.1983330. Epub 2021 Oct 6. Tissue Barriers. 2022. PMID: 34615441 Free PMC article.
-
Magnesium Isoglycyrrhizinate Alleviates Arsenic Trioxide-Induced Cardiotoxicity: Contribution of Nrf2 and TLR4/NF-κB Signaling Pathway.Drug Des Devel Ther. 2021 Feb 12;15:543-556. doi: 10.2147/DDDT.S296405. eCollection 2021. Drug Des Devel Ther. 2021. PMID: 33603344 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous
