Pteisolic acid G, a novel ent-kaurane diterpenoid, inhibits viability and induces apoptosis in human colorectal carcinoma cells
Pteisolic acid G, a novel ent-kaurane diterpenoid, inhibits viability and induces apoptosis in human colorectal carcinoma cells
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Pteisolic Acid G 是一种新型对映贝壳杉烷二萜类化合物，可抑制人结直肠癌细胞的活力并诱导细胞凋亡。
DOI：
10.3892/ol.2017.6889
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发表时间：
2017-11-01
期刊：
影响因子：
2.9
通讯作者：
Zhu, Xiaohui
中科院分区：
文献类型：
--
作者：
Qiu, Shuangli;Wu, Xin;Zhu, Xiaohui
人类结直肠癌（CRC）是癌症发病和死亡的主要原因，其发病率在全球经济转型地区不断增加。为了开发有效的结直肠癌化疗药物，本研究从 Pteris semipinnata 中分离并鉴定了一种新型对映贝壳杉烷二萜，称为翼蝶酸 G (PAG)。使用 Cell Counting Kit-8 测定法测定，这种对映贝壳杉烷二萜类化合物能够以时间和剂量依赖性方式显着抑制人 CRC HCT116 细胞的生长。此外，蛋白质印迹分析、Hoechst 33342染色和流式细胞术分析表明，PAG不仅通过抑制杂乱片段极性蛋白2/糖原合酶激酶3 β/β-catenin通路来抑制HCT116细胞的活力，而且还通过下调核因子-κB p65活性、刺激p53表达和促进细胞内活性氧的产生来诱导HCT116细胞凋亡。这些结果表明，PAG是一种新型Wnt/β-连环蛋白途径抑制剂和细胞凋亡诱导剂，应该通过体内实验和综合机制研究进行更详细的研究，以检验PAG作为治疗结直肠癌的新型治疗剂的潜在用途。
Human colorectal cancer (CRC) is a major cause of cancer morbidity and mortality, and its incidence rates are increasing in economical transitioning areas globally. To develop efficient chemotherapy drugs for CRC, the present study isolated and identified a novel ent-kaurane diterpenoid from Pteris semipinnata, termed pterisolic acid G (PAG). This ent-kaurane diterpenoid was demonstrated to significantly inhibit the growth of human CRC HCT116 cells in a time- and dose-dependent manner, determined using the Cell Counting Kit-8 assay. Additionally, western blot analysis, Hoechst 33342 staining and cytometry analysis revealed that PAG not only inhibited the viability of HCT116 cells by suppressing the dishevelled segment polarity protein 2/glycogen synthase kinase 3 β/β-catenin pathway, but also induced the apoptosis of HCT116 cells by downregulating nuclear factor-κB p65 activity, stimulating p53 expression and promoting the generation of intracellular reactive oxygen species. These results suggest that PAG, a novel inhibitor of the Wnt/β-catenin pathway and inducer of apoptosis, should be investigated in more detail using in vivo experiments and comprehensive mechanistic studies in order to examine the potential use of PAG as a novel therapeutic agent for the treatment of CRC.