Solasodine inhibited the proliferation of gastric cancer cells through suppression of Hedgehog/Gli1 signaling.

In this study, we investigated the beneficial effect of solasodine, a steroidal alkaloid from Solanaceae plants, on suppressing the proliferation of gastric cancer cells by targeting Hedgehog (Hh) signaling. Solasodine inhibited the proliferation of AGS and MKN74 gastric cancer cells and regulated cell cycle (Cyclin D1 and p27) and apoptosis (Bax and Bcl-2) markers in a dose-dependent manner, consistent with the Gli1/2 inhibitor Gant61 but not the Smo inhibitor vismodegib. As an upstream regulator, solasodine inhibited Hh signaling by down-regulating Gli1 expression and blocking its nuclear localization without affecting Smo levels. Molecular docking revealed stable binding of solasodine to Gli1, with a binding affinity of -7.4 kcal/mol. Moreover, solasodine inhibited Gli1 rather than Smo expression in Hh signaling overexpressed Ptch (-/-) MEF cells. Our findings demonstrate that solasodine inhibits gastric cancer proliferation by targeting Hh/Gli1 signaling, underscoring its potential as a potent agent for prevention and/or inhibition of gastric cancer.