Garcinone C Suppressed the Proliferation of Gastric Cancer Cells Through Regulating Hedgehog Signaling

Garcinone C, a xanthone derived from Garcinia mangostana L, possesses antioxidant and anticancer effects. However, its role in gastric cancer remains unexplored. This study aimed to investigate the effects of garcinone C on gastric cancer cell proliferation and its underlying mechanism. We found that garcinone C suppressed gastric cancer cell growth by inducing G0/G1 arrest and apoptosis in a dose‐dependent manner. Furthermore, garcinone C downregulated G0/G1 phase markers cyclin D1 and p21, as well as apoptosis markers Bax, Bcl‐2, cleaved‐PARP, and c‐caspase 3. Following the previous evidence demonstrated that aberrant Hedgehog (Hh) signaling is implicated in gastric cancer development, we confirmed that inhibiting Gli1/2 reduced the growth of AGS and MKN74 cells. Furthermore, garcinone C exerted similar effects to Gant61, inhibiting Hh signaling by reducing Gli1/2 levels and blocking their nuclear translocation. These findings suggest that garcinone C inhibits gastric cancer proliferation via the Hh signaling, indicating its potential as a therapeutic agent for treating gastric cancer.