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International Journal of Pharmacology
 
Defensive Mechanism in Human Cholangiocarcinoma Cells Against Hypoxia by Cyanidin-3-glucoside Treatment
Guang-Hua Xie, Wei Xie, Heyun Piao and Dan Li

Abstract:
Background and Objective: Cyanidin-3-glucoside (C3G) is one of the major bioactive compounds in anthocyanins, which have been shown to prevent a large spectrum of diseases. It has been reported that hypoxia is a common characteristic of many types of solid tumor and that the hypoxia-inducible factor 1α (HIF-1α) plays an important role in the process of angiogenesis and metastasis in cancer cells. The objective of this study was to explore the effects of C3G on HIF-1α activation in cholangiocarcinoma (CCA) cells. Materials and Methods: The human cholangiocarcinoma cell line QBC939 was used in this study. Hypoxic conditions were achieved by using the chemical hypoxia agent cobalt chloride or incubation at 1% O2. and MTT assay, Luciferase reporter assay, flow cytometric apoptosis assay, western blot, RT-PCR and immuno fluorescence methods were used to determine the C3G efficacy. Results: C3G markedly decreased the hypoxia-induced accumulation of HIF-1α reporter activity and protein expression in a dose-dependent manner and exerted a large apoptotic effect in CCA cells. Furthermore, C3G reduced expression of several genes downstream of HIF-1α, such as vascular endothelial growth factor and erythropoietin, without affecting the expression level of HIF-1α mRNA, thus indicating that C3G acts as an inhibitor of HIF-1α mRNA translation. Conclusion: This study provides a novel strategy to develop a low toxicity, high efficiency and multi-target natural active substance for the treatment of cancers.
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