Alterations of cellular organelles in human liver-derived hepatoma G2 cells induced by adriamycin

Abstract

Adriamycin (ADM) is a commonly used chemotherapeutic drug in the treatment of hepatocellular carcinoma. However, the mechanisms involved in ADM-induced cell death and the molecular basis of ADM resistance are still unclear. To observe the early events that occurred in hepatoma cells in response to ADM, we investigated the alterations of morphology and subcellular distributions of cellular organelles in human liver-derived hepatoma G2 (HepG2) cells after ADM treatment. HepG2 cells were exposed to different doses of ADM for up to 60 h. Cytotoxicity occurred 24 h after 0.05 microg/ml ADM application, and remaining living cells showed irregular shapes but continued to multiply. Some cellular organelles altered their subcellular distribution or morphology after ADM treatment, including mitochondria, autophagic vacuoles, and Golgi apparatus. Immunoblotting with anti-LC3 antibody showed the upregulation of LC3-II protein, confirming that ADM leads to the induction of autophagy in HepG2 cells. Our findings suggest that among most of the cellular organelles, mitochondria and autophagic vacuoles were involved in the early ADM response, and may contribute to ADM-induced HepG2 cell death.