title: Hydroxytyrosol inhibits cholangiocarcinoma tumor growth: an in vivo and in vitro study.
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.
authors.affiliation: 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.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Han
authors.forename: Yong
authors.initials: Y
authors.lastname: Ma
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Song
authors.forename: Tiemin
authors.initials: T
authors.lastname: Pei
authors.forename: Tongsen
authors.initials: T
authors.lastname: Zheng
authors.forename: Jiabei
authors.initials: J
authors.lastname: Wang
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Xu
authors.forename: Xiang
authors.initials: X
authors.lastname: Fang
authors.forename: Hongchi
authors.initials: H
authors.lastname: Jiang
authors.forename: Lianxin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001650:Bile Duct Neoplasms / Q000188:drug therapy; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D005706:Gallbladder Neoplasms / Q000188:drug therapy*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000975:Antioxidants; C005975:3,4-dihydroxyphenylethanol; D048049:Extracellular Signal-Regulated MAP Kinases; D010626:Phenylethyl Alcohol