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首页> 外文期刊>Journal of Cellular Physiology >Justicidin A-Induced Autophagy Flux Enhances Apoptosis of Human Colorectal Cancer Cells via Class III PI3K and Atg5 Pathway
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Justicidin A-Induced Autophagy Flux Enhances Apoptosis of Human Colorectal Cancer Cells via Class III PI3K and Atg5 Pathway

机译：Justicidin A-Induced自噬通量提高人类通过大肠癌细胞的细胞凋亡第三类PI3K和Atg5通路

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摘要

Our previous reports showed that justicidin A (JA), a novel and pure arylnaphthalide lignan isolated from Justicia procumbens, induces apoptosis of human colorectal cancer cells and hepatocellular carcinoma cells, leading to the suppression of both tumor cell growth in NOD-SCID mice. Here, we reveal that JA induces autophagy in human colorectal cancer HT-29 cells by conversion of autophagic marker LC3-I to LC3-II. Furthermore, LC3 puncta and autophagic vesicle formation, and SQSTM1/p62 suppression were observed. Administration of autophagy inhibitor (bafilomycin A1 and chloroquine) and transfection of a tandem fluorescent-tagged LC3 (mRFP-GFP) reporter plasmid (ptfLC3) demonstrated that JA induces autophagy flux in HT-29 cells. Expression of LC3, SQSTM1, Beclin 1, and nuclear DNA double-strand breaks (representing apoptosis) were also detected in the tumor tissue of HT-29 cells transplanted into NOD-SCID mice orally administrated with JA. In addition, the expression of autophagy signaling pathway-related molecules p-PDK1, p-mTOR, p-p70S6k/p-RPS6KB2 was decreased, whereas that of class III PI3K, Beclin 1, Atg5-Atg12, and mitochondrial BNIP3 was increased in response to JA. Pre-treatment of the cells with class III PI3K inhibitor 3-methyladenine or Atg5 shRNA attenuated JA-induced LC3-II expression and LC3 puncta formation, indicating the involvement of class III PI3K and Atg5. A novel mechanism was demonstrated in the anticancer compound JA; pre-treatment with 3-methyladenine or Atg5 shRNA blocked JA-induced suppression in cell growth and colony formation, respectively, via inhibition of apoptosis. In contrast, administration of apoptosis inhibitor Z-VAD did not affect JA-induced autophagy. Our data suggest the chemotherapeutic potential of JA for treatment of human colorectal cancer. (C) 2014 Wiley Periodicals, Inc.
机译：我们之前的报告显示,justicidin(是的),小说和纯arylnaphthalide木酚素从爵床分离procumbens,诱发人类大肠癌细胞的凋亡肝癌细胞,导致的在NOD-SCID抑制肿瘤细胞生长的老鼠。在人类大肠癌HT-29细胞自噬转换标记LC3-I LC3-II。此外,LC3 puncta和自噬囊泡形成和SQSTM1 / p62抑制观察到。(bafilomycin A1和氯喹)和转染串联的荧光标记LC3 (mRFP-GFP)记者质粒(ptfLC3)表明,农协在HT-29细胞诱导自噬流量。LC3、SQSTM1 Beclin 1,核DNA双链断裂(代表凋亡)也检测到肿瘤组织的HT-29吗细胞移植到小鼠NOD-SCID口服药与JA管理。自噬信号pathway-related的表情分子p-PDK1 p-mTOR p-p70S6k / p-RPS6KB2减少,而第三类PI3K Beclin1、Atg5-Atg12和线粒体BNIP3为了应对JA增加。细胞与第三类PI3K抑制剂3-methyladenine或Atg5 shRNA减毒JA-induced LC3-II表达和LC3 puncta形成,说明类的参与三世PI3K和Atg5。在抗癌化合物JA证明;预处理3-methyladenine或Atg5成分在细胞生长和阻止JA-induced抑制通过抑制分别集落形成细胞凋亡。细胞凋亡抑制剂Z-VAD没有影响JA-induced自噬。化疗是治疗的潜力人类结肠直肠癌。期刊、公司。

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