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Published on: January 31, 2025
Garcinone C suppresses colon tumorigenesis through the Gli1-dependent hedgehog signaling pathway
Jing Chen1, Shuai Qiu1, Jin Tae Kim1
1Department of Food Science and Biotechnology, Chung-Ang University, Anseong, 17546, South Korea.
Background:
Although garcinone C, a natural xanthone derivative identified in the pericarp of Garcinia mangostana, has been demonstrated to exert different health beneficial activities in oxidative stress and β-amyloid aggregation, the role of garcinone C in colon tumorigenesis has not been investigated. In addition, aberrant Hedgehog (Hh) signaling activation is associated with tumorigenesis including colon cancer. Here, we hypothesized that garcinone C can prevent colon tumorigenesis through regulating the Hh signaling pathway.
Method:
Colony formation assay and flow cytometry were used to evaluate the effect of garcinone C on the proliferation and cell cycle progression of colon cancer cells. Protein expression of cell cycle related markers and Hh/Gli1 signaling mediators were determined. The regulatory effect of orally administered garcinone C on the Hh/Gli1 signaling pathway and colon tumorigenesis was evaluated in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon cancer animal model.
Results:
Garcinone C suppressed the proliferation of colon cancer cells, induced G0/G1 cell cycle arrest, as well as regulated the expression of cell cycle-related markers such as cyclin D1, cyclin E, CDK6, and p21. Garcinone C inhibited the expression of Gli1, a key mediator of Hedgehog signaling, and protein kinase B (AKT) phosphorylation in Smo-independent colon cancer cells. In the AOM/DSS-induced colon tumorigenesis model, garcinone C significantly inhibited tumor development, regulated the expression of cell cycle markers and Gli1, and reduced AKT phosphorylation in colon tumor tissues, which is consistent with our in vitro results.
Conclusion:
Garcinone C can suppress colon tumorigenesis in vitro and in vivo through Gli1-dependent non-canonical Hedgehog signaling, suggesting that it may serve as a potent chemopreventive agent against colon tumorigenesis.
Insights
Garcinone C, a natural compound, inhibits colon cancer cell growth and tumor development by regulating Hedgehog signaling. This suggests its potential as a colon cancer chemopreventive agent.
Area of Science:
- Natural product chemistry
- Cancer biology
- Molecular signaling pathways
Background:
- Garcinone C, derived from Garcinia mangostana, shows antioxidant and anti-amyloid properties.
- The role of garcinone C in colon tumorigenesis remains unexplored.
- Aberrant Hedgehog (Hh) signaling is implicated in colon cancer development.
Purpose of the Study:
- To investigate the potential of garcinone C in preventing colon tumorigenesis.
- To elucidate the mechanism by which garcinone C affects colon cancer, focusing on the Hh signaling pathway.
Main Methods:
- In vitro studies using colony formation and flow cytometry assays to assess garcinone C's effects on colon cancer cell proliferation and cell cycle.
- Analysis of cell cycle and Hh/Gli1 signaling pathway protein expression.
- In vivo evaluation in an azoxymethane/dextran sulfate sodium-induced mouse model of colon cancer.
Main Results:
- Garcinone C suppressed colon cancer cell proliferation and induced G0/G1 cell cycle arrest.
- It downregulated Gli1 expression and AKT phosphorylation in Smo-independent colon cancer cells.
- In vivo, garcinone C inhibited tumor development and modulated cell cycle markers and Gli1 expression.
Conclusions:
- Garcinone C suppresses colon tumorigenesis via Gli1-dependent non-canonical Hedgehog signaling.
- Garcinone C demonstrates potential as a chemopreventive agent against colon cancer.
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