Anthricin-induced caspase-dependent apoptosis through IGF1R/PI3K/AKT pathway inhibition in A549 human non-small lung cancer cells

Abstract

Anthricin (deoxypodophyllotoxin) is a major lignan in Anthriscus sylvestris and possesses many bioactivities such as antiproliferative, antitumor, anti-platelet aggregation, antiviral and anti-inflammatory actions. However, the anticancer effects of anthricin on A549 human non-small cell lung cancer cells and potential molecular mechanisms remain unknown. Therefore, we investigated the anticancer effect of anthricin and the underlying mechanism in A549 cells. Anthricin (10-200 nM) inhibited the viability of A549 cells in a dose- and time-dependent manner. Moreover, anthricin-induced apoptosis was confirmed by live and dead assay, 4,6-dianmidino-2-phenylindole staining, and flow cytometric analysis. In addition, anthricin induced cell cycle arrest at the G2/M phase through suppression of the expression of cell cycle cascade proteins, Cdc2 and Cdc25C. Furthermore, it induced the expression of caspase-related proteins and significantly suppressed the phosphorylation of insulin-like growth factor 1 receptor (IGF1R), PI3K and Akt. Anthricin significantly inhibited tumor growth without any significant change in the body weight of mice in A549 tumor xenograft BALB/c nude mice. Anthricin induced caspase-dependent apoptosis through the IGF1R/PI3K/Akt signaling pathway in A549 cells.