Abstract

Cholangiocarcinoma (CCA) is biliary tract malignancy. Because no specific biomarkers are available, CCA patients frequently present with disseminated tumour that is too late for curative treatment, leading to a high mortality rate. Honokiol and magnolol are the hydroxylated biphenyl compounds isolated from Magnolia officinalis. Many studies have reported that honokiol and magnolol have antitumour effects on various types of cancer, but the evidence of the effects of these compounds on CCA cells has not yet been reported. This study therefore aims to evaluate the antitumour activities of honokiol and magnolol on CCA cell lines. The CCA cell lines were incubated with honokiol and magnolol before determining their responses. The results indicate that low concentrations of honokiol and magnolol suppressed CCA proliferation by induction of cell cycle arrest at G0/G1 and down-regulation of cyclin D1 protein. Moreover, these compounds exhibited an antimetastasis ability mediated by inhibiting migration, adhesion, and the MMP activities of CCA cells. In addition, at high concentrations of honokiol and magnolol activated CCA cell death associated with the apoptosis signalling pathway, along either an intrinsic or extrinsic pathway. Our data provides evidence that honokiol and magnolol have potential anticancer properties and are promising compounds for alternative CCA treatment.

Highlights

  • IntroductionThe results indicate that low concentrations of honokiol and magnolol suppressed CCA proliferation by induction of cell cycle arrest at G0/G1 and down-regulation of cyclin D1 protein

  • The IC50 of honokiol and magnolol on treated MMNK-1 cell line was higher than the CCA cell lines (Table 1), which suggests that these compounds showed less cytotoxicity in human cholangiocyte

  • The results of this study showed that honokiol and magnolol significantly suppress the proliferation ability of CCA cells, while they exhibit less cytotoxicity in immortalized cholangiocyte

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Summary

Introduction

The results indicate that low concentrations of honokiol and magnolol suppressed CCA proliferation by induction of cell cycle arrest at G0/G1 and down-regulation of cyclin D1 protein. These compounds exhibited an antimetastasis ability mediated by inhibiting migration, adhesion, and the MMP activities of CCA cells. This study reports the antitumour activities of honokiol and magnolol on Opisthorchis viverrini- associated human CCA cell lines, KKU-100 and KKU-213L5. We demonstrate that these compounds inhibit cell proliferation as well as suppress the cancer cell metastasis ability. Our data indicates that honokiol and magnolol are potential therapeutic agents for CCA patients

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