Targeting signal transducer and activator of transcription 3 contributes to the solamargine-inhibited growth and -induced apoptosis of human lung cancer cells

Solamargine (SM), a major steroidal alkaloid glycoside extracted from a traditional Chinese medicinal herb, Solanum nigrum L. (SNL), has been shown to inhibit growth and induce apoptosis of various cancer cells. However, the molecular mechanisms underlying this are poorly understood. In this study, we showed that SM inhibited growth and induced apoptosis of non-small-cell lung cancer (NSCLC) cells in a time- and dose-dependent manner. To further explore this, we found that SM increased phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in a time-dependent fashion. SM also inhibited phosphorylation and protein expression of signal transducer and activator of transcription 3 (Stat3), a transcription factor, which was abrogated by the SB203580, a specific inhibitor of p38 MAPK. In addition, SM induced protein expression of p21, one of cyclin-dependent kinase inhibitors, and this was not observed in cell overexpression of Stat3 or cells treated with SB203580. Finally, while silencing of Stat3 had no further effect, exogenous expression of Stat3 overcame the effect of SM on cell proliferation. Collectively, our results show that SM inhibits proliferation and induces apoptosis in lung cancer cells through p38 MAPK-mediated suppression of phosphorylation and protein expression of Stat3, followed by inducing Stat3 downstream effector p21. This unveils a potential new mechanism by which SM inhibits growth of human lung cancer cells.