Cell type-dependent effects of andrographolide on human cancer cell lines

Aims: Andrographolide (ANDRO) is emerging as a promising anti-tumour compound. While it causes apoptosis in most cancer cells, andrographolide induces cell cycle arrest in hepatocellular cancer lines. In this study, we studied the effect of andrographolide on hepatocellular cancers and other cancer types, and elucidated the possible hepatoma-specific features of andrographolide toxicity. Main methods: We compared the responses of a panel of human cell lines to andrographolide treatment by using flow cytometry, cell synchronisation and time-lapse microscopy. We have also examined their expression of cell cycle-related proteins and proteome changes after andrographolide treatment. Key findings: Andrographolide exerts its effect on hepatocellular cancer cells through cell cycle arrest and not apoptosis. In HepG2 cells, it blocks G2 cells from entering mitosis and prevents mitosis from completion. This might be due to the disruption of mitotic spindle during metaphase. Despite the dramatic differences in their responses to andrographolide, HepG2 and HeLa cells display similar biochemical consequences. Andrographolide induces DNA damages, as indicated by the expression of phospho-H2AX in both cell lines. Proteomic experiments show that heme oxygenase 1 and heat shock protein 70 are among the proteins induced by andrographolide, which indicate the possible role of oxidative stress in the anti-cancer mechanism of this drug. Significance: Andrographolide can invoke different cellular responses depending on the biochemical and physiological context in different cell and cancer types, and reveal an additional dimension of the therapeutic applications of this compound. (C) 2012 Elsevier Inc. All rights reserved.