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苍术素和β-桉叶醇对胆管癌细胞系的细胞毒性活性、细胞周期阻滞及凋亡的影响

Cytotoxic activities and effects of atractylodin and β-eudesmol on the cell cycle arrest and apoptosis on cholangiocarcinoma cell line.

作者信息

Kotawong Kanawut, Chaijaroenkul Wanna, Muhamad Phunuch, Na-Bangchang Kesara

机构信息

Chulabhorn International College of Medicine, Thammasat University, Paholyothin Road, Klonglung, Pathum Thani, 12120, Thailand.

Drug Discovery and Development Center, Thammasat University, Paholyothin Road, Klonglung, Pathum Thani, 12120, Thailand.

出版信息

J Pharmacol Sci. 2018 Feb;136(2):51-56. doi: 10.1016/j.jphs.2017.09.033. Epub 2018 Jan 12.

Abstract

Cholangiocarcinoma (CCA) is the cancer of bile duct with high mortality rate particularly in Thailand. The clinical efficacy of the standard chemotherapeutics remains unsatisfactory, and therefore, discovery and development of the new alternative drugs with high efficacy and tolerability is needed. The aim of the study was to investigate cytotoxic activity as well as the underlying mechanisms through which atractylodin and β-eudesmol exert their activities on CCA cell growth inhibition, cell cycle arrest, and cell apoptosis. Effects of the compounds on cell cytotoxicity, cell cycle arrest, and cell apoptosis were analyzed using MTT assay, BD Cycletest™ Plus DNA kit, and FITC Annexin V Apoptosis Detection Kit I, respectively. The cytotoxic activities of both compounds were concentration- and time-dependent. The IC [mean (SD)] of atractylodin and β-eudesmol were 41.66 (2.51) and 39.33 (1.15) μg/ml respectively. Both promoted cell cycle arrest at G1 phase, and induced cell apoptosis through activation of caspase-3/7. The highest activity was observed at 48 h of exposure. Results suggest that these mechanisms are at least in part, explain the cell cytotoxic and anti-CCA activity of atractylodin and β-eudesmol shown in vitro and in vivo models.

摘要

胆管癌(CCA)是一种胆管癌症,死亡率很高,在泰国尤为如此。标准化疗药物的临床疗效仍然不尽人意,因此,需要发现和开发具有高效性和耐受性的新型替代药物。本研究的目的是研究苍术素和β-桉叶醇对CCA细胞生长抑制、细胞周期阻滞和细胞凋亡的细胞毒活性及其潜在机制。分别使用MTT法、BD Cycletest™ Plus DNA试剂盒和FITC Annexin V凋亡检测试剂盒I分析化合物对细胞毒性、细胞周期阻滞和细胞凋亡的影响。两种化合物的细胞毒活性均呈浓度和时间依赖性。苍术素和β-桉叶醇的IC[平均值(标准差)]分别为41.66(2.51)和39.33(1.15)μg/ml。两者均促进细胞周期阻滞于G1期,并通过激活caspase-3/7诱导细胞凋亡。在暴露48小时时观察到最高活性。结果表明,这些机制至少部分解释了苍术素和β-桉叶醇在体外和体内模型中表现出的细胞毒和抗CCA活性。

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