Narahara Chisato, Saeheng Teerachat, Chaijaroenkul Wanna, Dumre Shyam Prakash, Na-Bangchang Kesara, Karbwang Juntra
Department of Clinical Product Development, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Graduate Studies, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand.
J Res Med Sci. 2020 Jan 20;25:7. doi: 10.4103/jrms.JRMS_291_19. eCollection 2020.
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.
Two CCA cell lines (HuH28 and HuCCT1) were assessed at different time points after β-eudesmol treatment for mRNA and protein expression profiles of , and by real-time polymerase chain reaction and western blot, respectively.
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.
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.
胆管癌(CCA)是一种在发展中国家普遍存在且负担重、死亡率高的被忽视疾病,并且尚无有效治疗方法。我们旨在利用凋亡途径的选定关键分子,研究β-桉叶醇在人CCA细胞系中的分子作用靶点。
分别通过实时聚合酶链反应和蛋白质印迹法,在β-桉叶醇处理后的不同时间点评估两种CCA细胞系(HuH28和HuCCT1)中 、 和 的mRNA和蛋白质表达谱。
β-桉叶醇在HuH28和HuCCT1细胞中诱导p21和p53在mRNA/蛋白质水平的表达。在β-桉叶醇处理后,这些CCA细胞还表达了caspase-3、-8、-9和bax(mRNA和/或蛋白质水平)等,表明其在内在和外在的caspase依赖性凋亡途径中均起作用。
该研究表明β-桉叶醇诱导凋亡途径蛋白的表达,提示其在促进caspase依赖性凋亡途径以及诱导CCA细胞系细胞周期停滞方面的潜在作用。β-桉叶醇可被视为一种有潜力的化合物,作为抗CCA药物有待进一步研究。