2. Academic Validation
  3. Garcinone C suppresses colon tumorigenesis through the Gli1-dependent hedgehog signaling pathway

Garcinone C suppresses colon tumorigenesis through the Gli1-dependent hedgehog signaling pathway

  • Phytomedicine. 2020 Dec:79:153334. doi: 10.1016/j.phymed.2020.153334.
Jing Chen 1,  Shuai Qiu 1,  Jin Tae Kim 1,  Jae Seok Cho 1,  Ji Hyun Moon 1,  Yimeng Zhou 1,  Joong-Hyuck Auh 2,  Hong Jin Lee 3
Affiliations

Affiliations

  • 1 Department of Food Science and Biotechnology, Chung-Ang University, Anseong, 17546, South Korea.
  • 2 Department of Food Science and Biotechnology, Chung-Ang University, Anseong, 17546, South Korea. Electronic address: jhauh@cau.ac.kr.
  • 3 Department of Food Science and Biotechnology, Chung-Ang University, Anseong, 17546, South Korea. Electronic address: hongjin@cau.ac.kr.
PMID: 32920288 DOI: 10.1016/j.phymed.2020.153334
Abstract

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.

Keywords

Colon cancer; Garcinone C; Gli1; Hedgehog signaling; Protein kinase B.

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