Action of solamargine on human lung cancer cells – enhancement of the susceptibility of cancer cells to TNFs

Solamargine (SM), isolated from Solanum incanum herb, displayed a superior cytotoxicity in four human lung cancer cell lines. The half-inhibitory concentrations (IC₅₀), of the cell viability assay for H441, H520, H661 and H69 cells were 3, 6.7, 7.2 and 5.8 μM, respectively. SM-induced apoptosis of these cells by PS externalization in a dose-dependent manner and increased sub-G₁ fraction were observed. Quenching of the expression of tumor necrosis factor receptors (TNFRs) during the progress of human lung carcinogenesis has been previously reported. SM may induce cell apoptosis via modulating the expression of TNFRs and their subsequent TRADD/FADD signal cascades. Subsequently, SM treatment increased the binding activities of TNF-α and TNF-β to the lung cancers, and the intrinsic TNFs-resistant cancer cells became susceptible to TNF-α and -β. In addition, SM caused release of cytochrome c, downregulation of anti-apoptotic Bcl-2 and Bcl-x_L, increase of caspase-3 activity, and DNA fragmentation. Thus, SM could modulate the expressions of TNFRs and Bcl-2, and might be a potential anticancer agent for TNFs and Bcl-2 related resistance of human lung cancer cells. [Copyright &y& Elsevier]