Parthenolide-induced cytotoxicity in H9c2 cardiomyoblasts involves oxidative stress

Tien Yao Tsai, Paul Chan, Chi Li Gong, Kar Lok Wong, Tzu Hui Su, Pei Chen Shen, Yuk Man Leung, Zhong Min Liu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Cardiac cellular injury as a consequence of ischemia and reperfusion involves nuclear factor-κB (NF-κB), amongst other factors, and NF-κB inhibitors could substantially reducemyocardial infarct size. Parthenolide, a sesquiterpene lactone compound which could inhibit NF-κB, has been shown to amelioratemyocardial reperfusion injury but may also produce toxic effects in cardiomyocytes at high concentrations. The aim of this study was to examine the cytotoxic effects of this drug on H9c2 cardiomyoblasts, which are precursor cells of cardiomyocytes. Method: Cell viability and apoptosis were examined by MTT and TUNEL assay, respectively, and protein expression was analyzed by western blot. Reactive oxygen species (ROS) production was measured using DCFH-DA as dye. Cytosolic Ca2+ concentration and mitochondrial membrane potential were measured microfluorimetrically using, respectively, fura 2 and rhodamine 123 as dyes. Results : Parthenolide caused apoptosis at 30 μM, as judged by TUNEL assay and Bax and cytochrome c translocation. It also caused collapse of mitochondrial membrane potential and endoplasmic reticulum stress. Parthenolide triggered ROS formation, and vitamin C (antioxidant) partially alleviated parthenolide-induced cell death. Conclusions: The results suggested that parthenolide at high concentrations caused cytotoxicity in cardiomyoblasts in part by inducing oxidative stress, and demonstrated the imperative for cautious and appropriate use of this agent in cardioprotection.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalActa Cardiologica Sinica
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Keywords

  • Cardiomyoblast
  • Endoplasmic reticulum stress
  • Oxidative stress
  • Parthenolide
  • Reperfusion injury

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Tsai, T. Y., Chan, P., Gong, C. L., Wong, K. L., Su, T. H., Shen, P. C., Leung, Y. M., & Liu, Z. M. (2015). Parthenolide-induced cytotoxicity in H9c2 cardiomyoblasts involves oxidative stress. Acta Cardiologica Sinica, 31(1), 33-41. https://doi.org/10.6515/ACS20140422B