Growth inhibitory effect of β-eudesmol on cholangiocarcinoma cells and its potential suppressive effect on heme oxygenase-1 production, STAT1/3 activation, and NF-κB downregulation.

Abstract:

:Cholangiocarcinoma (CCA) is a progressively fatal form of cancer originating from the malignant transformation of hepatic biliary cholangiocytes. The present study reports for the first time in vitro growth inhibitory activities of β-eudesmol, the bioactive sesquiterpenoid present in the rhizome of Atractylodes lancea (Thunb) DC., with respect to its underlying potential effects on heme oxygenase-1 (HO-1) production, STAT1/3 phosphorylation, and NF-κB protein expression in human CCA cell line CL-6. The cytotoxic effect of β-eudesmol on CL-6 cells was evaluated by MTT assay using normal human embryonic fibroblast (OUMS) as a control cell line. Results indicated that β-eudesmol exhibited selective cytotoxicity towards CL-6 compared to OUMS with mean (±SD) IC50 (concentration that inhibits cell growth by 50%) values of 166.75 ± 3.69 and 240.01 ± 16.54 μmol/L, respectively. In addition, it also significantly suppressed colony forming and wound healing ability of CL-6 cells in a concentration-dependent manner. Western blot analysis indicated that β-eudesmol treatment resulted in significant suppression of HO-1 production in CL-6 cells. Its inhibitory effects on the phosphorylation of STAT1/3 proteins and expression of NF-κB (p65 and p50) proteins were concentration-dependent. Taken together, these results suggest that β-eudesmol exerts significant growth inhibitory activity on CL-6 cells that may be linked to its inhibitory effect on the production of HO-1, phosphorylation of STAT1/3, and expression of major NF-κB proteins.

authors

Mathema VB,Chaijaroenkul W,Karbwang J,Na-Bangchang K

doi

10.1111/1440-1681.12818

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

1145-1154

issue

11

eissn

0305-1870

issn

1440-1681

journal_volume

44

pub_type

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