Justicidin A-Induced autophagy flux enhances apoptosis of human colorectal cancer cells via class III PI3K and Atg5 pathway

Shen Jeu Won, Cheng Hsin Yen, Hsiao Sheng Liu, Shan Ying Wu, Sheng Hui Lan, Ya Fen Jiang-Shieh, Chun Nan Lin, Chun Li Su*


研究成果: 雜誌貢獻期刊論文同行評審

36 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)930-946
期刊Journal of Cellular Physiology
出版狀態已發佈 - 2015 4月 1

ASJC Scopus subject areas

  • 生理學
  • 臨床生物化學
  • 細胞生物學


深入研究「Justicidin A-Induced autophagy flux enhances apoptosis of human colorectal cancer cells via class III PI3K and Atg5 pathway」主題。共同形成了獨特的指紋。