Role of Glutathione-S transferase Pi (GSTπ) during the treatment of doxorubicin and the plant extract Phyllanthus urinaria L. in H9c2 cells

Doxorubicin (DOX) is widely used to treat many types of cancer but frequently causes cardiotoxicity [1]. Our previous study has shown that an extract from Phyllanthus urinaria (PU) protected against DOX-induced cytotoxicity in H9c2 cells [2]. In this study, we examined the mechanism of cytoprotection in association with the expression and localization of glutathione-S transferase in H9c2 cells. The expression of antioxidant enzymes including glutamylcysteine synthetase (GCS), MnSOD, and CuZnSOD was also investigated. We found that among three major GST subtypes GST Pi (GSTP) is predominantly expressed in H9c2 cells. While no significant alterations in the enzyme activities, the cytoprotective effect of PU treatment appeared to involve nuclear localization of GSTP. Using RNA interference technique to suppress GSTP expression provided evidence that DOX was highly accumulated in nuclei and apoptosis was increased as evaluated by TUNEL assay. In conclusion, PU may be used as an alternative resource of antioxidants with distinctive mechanisms of action that may be suitable for specific type of oxidative insults.

Acknowledgements: Srinakharinwirot University Research Fund; The Matsumae International Foundation

References: [1] Zunino, F. et al. (1990) Anticancer Drug Des 5:307–317.

[2] Chularojmontri, L. et al. (2005) Bio. Pharm. Bull. 28:1165–1171