in Vitro and in Vivo Inhibitory Effects of α-Mangostin on Cholangiocarcinoma Cells and Allografts

Document Type: Research Articles

Authors

1 Department of Thai Traditional Medicine, Faculty of Natural Resources, Rajamangala University of Technology Isan Sakonnakhon Campus, Sakon Nakhon 47160 Thailand

2 Neglected, Zoonosis and Vector-Borne Disease Group, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand

3 Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 Thailand

4 Liver Fluke and Cholangiocarcinoma Research Center, Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen 40002, Thailand

5 Department of Anesthesiology, , Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 Thailand

6 Department of Community Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 Thailand

7 Department of Parasitology Graduate School of Medicine Gifu University, Gifu, Japan

8 Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 Thailand

9 Department of Biochemistry,Faculty of Medicine, KhonKaen University, Khon Kaen 40002 Thailand

Abstract

 
We investigated the anti-cholangiocarcinoma effect of α-mangostin from Garcinia mangostana pericarp extract (GM) in a human cholangiocarcinoma (CCA) cell line and a hamster CCA allograft model. In vitro, human CCA cells were treated with GM at various concentrations and for different time periods; then cell-cycle arrest and apoptosis were evaluated using flow cytometry, and metastatic potential with wound healing assays. In vivo, hamster allografts were treated with GM, gemcitabine (positive control) and a placebo (negative control) for 1 month; tumor weight and volume were then determined. Histopathological features and immunostaining (CK19 and PCNA) characteristics were examined by microscopy. The present study found that α-mangostin could: inhibit CCA cell proliferation by inducing apoptosis through the mitochondrial pathway; induce G1 cell-cycle arrest; and inhibit metastasis. Moreover, α-mangostin could inhibit CCA growth, i.e. reduce tumor mass (weight and size) and alter CCA pathology, as evidenced by reduced positive staining for CK19 and PCNA. The present study thus suggested that α-mangostin is a promising anti-CCA compound whose ready availability in tropical countries might indicate use for prevention and treatment of CCA.

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