Premium
Insights into Anti Cancer Agent‐Induced Cardiotoxicity
Author(s) -
Weerasinghe Priya,
Brown Robert,
Buja L. Maximilian
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.137.9
Subject(s) - cardiotoxicity , sanguinarine , apoptosis , programmed cell death , pharmacology , cancer research , cell culture , cancer cell , cancer , cell , biology , microbiology and biotechnology , chemistry , toxicity , medicine , biochemistry , alkaloid , botany , genetics
Anti cancer therapy is often complicated by the development of toxicity to the heart. Cardiotoxicity due to anti neoplastic therapy is important to recognize and address as this may have a significant impact on the overall prognosis and survival of those patients. Recent studies have explored the relationship of cardiomyocyte cell injury to the major modes of cell death, and it appears that cardiomyocyte cell injury involves the pathways of apoptosis and oncosis. We have found sanguinarine, a known anticancer agent, to induce apoptosis and oncosis in several malignant cell lines when treated with concentrations of 1.5 μg/ml and 25 μg/ml, respectively. Furthermore, a similar biphasic pattern of cell death was observed when cultured primary cardiomyocytes were treated with the same sanguinarine concentrations. Using this primary cardiomyocyte cell model we proceeded to study the molecular expression profile of oncosis. Microarray analysis of 4 repeated experiments revealed altered expression of 2514 probes in sanguinarine‐induced oncosis (p value <0.001). The pathways involved include mitochondrial dysfunction, fatty acid metabolism, p53 signaling and oxidative phosphorylation. The discovery of novel oncosis‐related molecules could facilitate the development of more effective therapeutics to combat and prevent chemotherapeutic cardiotoxicity.