Hydroxytyrosol inhibits cholangiocarcinoma tumor growth: An in vivo and in vitro study

Li,Shuai; Han,Zhiyang; Ma,Yong; Song,Ruipeng; Pei,Tiemin; Zheng,Tongsen; Wang,Jiabei; Xu,Dongsheng; Fang,Xiang; Jiang,Hongchi; Liu,Lianxin

doi:10.3892/or.2013.2853

Hydroxytyrosol inhibits cholangiocarcinoma tumor growth: An in vivo and in vitro study

Authors:
- Shuai Li
- Zhiyang Han
- Yong Ma
- Ruipeng Song
- Tiemin Pei
- Tongsen Zheng
- Jiabei Wang
- Dongsheng Xu
- Xiang Fang
- Hongchi Jiang
- Lianxin Liu
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Affiliations: Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China, Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China
Published online on: November 14, 2013 https://doi.org/10.3892/or.2013.2853
Pages: 145-152

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Abstract

Cholangiocarcinoma (CCA) is a type of digestive tumor that is associated with a high rate of mortality due to the difficulty of early diagnosis and the resistance of this tumor type to chemotherapy. Hydroxytyrosol (HT), which is derived from virgin olive oil (VOO), has recently been reported to inhibit the proliferation of various types of human cancer cells. In the present study, we investigated the effect of HT on CCA. The antiproliferative and proapoptotic effects of HT on CCA were evaluated in the human CCA cell lines TFK-1 and KMBC and the human gallbladder cancer cell line GBS-SD. We also assessed this effect in vivo. We found that 75 µM HT inhibited the proliferation of the TFK-1, KMBC and GBS-SD cell lines. However, 200 µM HT treatment did not affect the proliferation of the human bile duct cell line HIBEpiC. More importantly, HT (250 and 500 mg/kg/day) markedly inhibited the growth of CCA xenografts in mice. G2/M phase cell cycle arrest and apoptosis were observed using flow cytometry and western blotting, and we also noted a time- and dose-dependent inhibition of phospho-ERK, with no changes in total-ERK, during treatment with HT. The present study showed that HT induces cell cycle arrest and apoptosis in vitro and in vivo. These data suggest that HT, which possesses excellent biocompatibility and few side-effects, could be developed as a novel agent against CCA.

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