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bioRxiv · 10.1101/2025.05.26.655423

Garcinone C suppressed the proliferation of gastric cancer cells through regulating Hedgehog signaling

Zhou, Y.·Kim, J. T.·Kwon, J. W.·Lee, G. Y.·Son, H. M.·Lee, K. H.·Qiu, S.·Lee, H. J.
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Abstract

Garcinone C, a xanthone derived from Garcinia mangostana L, possesses antioxidant and anti-cancer 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.

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Zhou, Y., Kim, J. T., Kwon, J. W., Lee, G. Y., Son, H. M., Lee, K. H., Qiu, S., Lee, H. J.. 2025-05-30. Garcinone C suppressed the proliferation of gastric cancer cells through regulating Hedgehog signaling. https://doi.org/10.1101/2025.05.26.655423

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