Andrographolide induces autophagic cell death in human liver cancer cells through cyclophilin D-mediated mitochondrial permeability transition pore

• DOI: 10.1093/carcin/bgs264
• Publication Date: 2012-08-07T00:35:15Z
• Authors: Wei Chen; Lina Feng; Hao Nie; Xiaodong Zheng
• Keywords: Andrographolide

Liver cancer is the third leading cause of death worldwide and about half patients with liver require adjuvant therapy after surgical resection. Therefore, development novel agents to eradicate cells may constitute a viable approach treat cancer. Andrographolide, diterpenoid lactone isolated from Andrographis paniculata , known possess potent antioxidant, anti-inflammatory, antineoplastic antiviral properties. In this study, we investigated cytotoxic effect andrographolide on human explored cell mechanism. Andrographolide induced distinct apoptosis in multiple cells. The was characterized by autophagy as evidenced accumulation LC3 II autophagosomes, formation puncta GFP-LC3. This well cytotoxicity caused could be effectively prevented 3-methyladenine (a chemical inhibitor autophagy). Mechanistic study indicated that autophagic disruption mitochondrial transmembrane potential elevation reactive oxygen species, which were correlated permeability transition pore Inhibition cyclophilin D component MPTP) cyclosporin A or abrogation its expression small interfering RNA significantly suppressed andrographolide, suggesting play an important role mediating andrographolide-induced cytotoxicity. Taken together, our findings unveil mechanism drug action suggest represent promising agent treatment