β-Eudesmol induces the expression of apoptosis pathway proteins in cholangiocarcinoma cell lines

Chisato Narahara; Teerachat Saeheng; Wanna Chaijaroenkul; Shyam Prakash Dumre; Kesara Na-Bangchang; Juntra Karbwang

doi:10.4103/jrms.JRMS_291_19

β-Eudesmol induces the expression of apoptosis pathway proteins in cholangiocarcinoma cell lines

J Res Med Sci. 2020 Jan 20:25:7. doi: 10.4103/jrms.JRMS_291_19. eCollection 2020.

Authors

Chisato Narahara¹, Teerachat Saeheng¹, Wanna Chaijaroenkul², Shyam Prakash Dumre³, Kesara Na-Bangchang^{2

4}, Juntra Karbwang^{1

4}

Affiliations

¹ Department of Clinical Product Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
² Graduate Studies, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.
³ Department of Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
⁴ Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.

Abstract

Background: Cholangiocarcinoma (CCA) is a neglected disease prevalent in developing countries with high burden and mortality rate, and there is no effective treatment. We aimed to investigate β-eudesmol molecular target of action in human CCA cell lines using the selected key molecules of apoptotic pathways.

Materials and methods: Two CCA cell lines (HuH28 and HuCCT1) were assessed at different time points after β-eudesmol treatment for mRNA and protein expression profiles of caspase-3, -8, -9, p53, p21, Bcl-2, and Bax by real-time polymerase chain reaction and western blot, respectively.

Results: β-eudesmol induced expressions of p21 and p53 in mRNA/protein level in HuH28 and HuCCT1 cells. These CCA cells also expressed caspase-3, -8, -9 and bax (mRNA and/or protein level) among others after β-eudesmol treatment indicating its role in both intrinsic and extrinsic caspase-dependent apoptotic pathways.

Conclusion: The study demonstrated that β-eudesmol induced the expression of apoptosis pathway proteins, suggesting its potential role in promoting the caspase-dependent apoptotic pathway, and induction of the cell cycle arrest in CCA cell lines. β-eudesmol can be considered as a potential compound for further investigation as an anti-CCA agent.

Keywords: Apoptosis; cholangiocarcinoma; mode of action; molecular targets; β-eudesmol.