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Article Publish Status: FREE
Abstract Title:

Xanthohumol chalcone acts as a powerful inhibitor of carcinogenesis in drug-resistant human colon carcinoma and these effects are mediated via G2/M phase cell cycle arrest, activation of apoptotic pathways

Abstract Source:

J BUON. 2019 Nov-Dec;24(6):2442-2447. PMID: 31983118

Abstract Author(s):

Xiaokang Liu, Li Juan An, Yu Li, Yanwei Wang, Lei Zhao, Xi Lv, Jinyi Guo, Ai Lin Song

Article Affiliation:

Xiaokang Liu

Abstract:

PURPOSE: Xanthohumol is a prenylated flavonoid of plant origin and has been reported to exhibit a spectrum of pharmacological properties including anticancer effects. However, the anticancer properties of Xanthohumol have not been thoroughly evaluated against drug-resistant colon cancer cells. This study was undertaken to evaluate the anticancer effects of Xanthohumol against the human colon cancer cell line HT-29 and normal CDD-18Co cell line.

METHODS: HT-29 cell viability was evaluated by cell counting kit-8 (CCK8) assay. Apoptotic effects were examined by fluorescence microscopy using DAPI staining and flow cytometry using annexin V/propidium iodide (PI) staining. Effects on cell cycle were studied by flow cytometry while western blot analysis was done to study effects on protein expressions.

RESULTS: The results showed that Xanthohumol causes a dramatic decrease in the HT-29 cell viability with an IC50 of 10µM. However, an IC50>100µM for Xanthohumol against the normal CDD-18Co cells suggested cancer cell specific activity. DAPI staining revealed nuclear fragmentation, suggesting xanthohumol induces apoptosis in HT-29 cells. Xanthohumol also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio. Cell cycle analysis showed that this molecule caused arrest of the HT-29 cells at the G2/M phase of the cell cycle. The induction of G2/M cell cycle was also accompanied with depletion of the expression of cyclin B1. The effects of Xanthohumol were also investigated on the Ras/MEK/ERK signalling pathway which revealed that Xanthohumol also blocks the MEK/ERK signalling pathway in colon cancer cells in a concentration-dependent manner.

CONCLUSIONS: Xanthohumol may prove an efficient lead molecule for the development of more potent anticancer agents through semi-synthetic approaches.

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Sayer Ji
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