The comparison analysis of polyphyllin I and its analogues induced apoptosis of colon and lung cancer cells via mitochondrial dysfunction

Abstract

Polyphyllin I (PPI) and its analogues, including polyphyllin II (PPII), polyphyllin VI (PPVI) and polyphyllin VII (PPVII), are major bioactive compounds isolated from the Chinese herb Chonglou. However, the susceptibilities of PPI and its analogues towards the different cell lines are diversified and the mechanisms are not fully clarified. Thus, the present study aimed to investigate the cytotoxicity of PPI and its analogues on two different cell lines, as well as to explore the underlying mechanisms of these agents via inducing mitochondrial dysfunction. The results showed that PPI and its analogues were cytotoxic agents towards both A549 and HT-29 cells, with IC₅₀ values ranged from 1.0 to 4.5 μmol/L. Further investigations demonstrated that they decreased the mitochondrial membrane potentials of both A549 and HT-29 cells in a dose-dependent manner. Among all tested compounds, PPVI and PPI induced the most obvious changes in Ca²⁺ haemostasis in these two cell lines. In addition, they could induce the accumulation of ROS in cells and down-regulated the Bcl-2 expression, up-regulated the Bax expression and induced the activity of cleaved caspase-3 in cells. Collectively, our findings clearly demonstrated the cytotoxic differences and mechanisms of PPI and its analogues induced cell apoptosis and could partially explain the anticancer effects of these natural constituents in Chonglou.

Keywords: Chonglou; cell apoptosis; comparison analysis; mitochondrial dysfunction; polyphyllin I and its analogues.