Clioquinol induces pro-death autophagy in leukemia and myeloma cells by disrupting the mTOR signaling pathway

作者: Biyin Cao , Jie Li , Xiumin Zhou , Jiaxiang Juan , Kunkun Han

DOI: 10.1038/SREP05749

关键词: PI3K/AKT/mTOR pathwaymTORC1Programmed cell deathCell biologyClioquinolCancer cellRPTORAutophagyApoptosisBiology

摘要: Clioquinol is an anti-microbial drug, and it was recently found to induce cancer cell death. In the present study, clioquinol trigger autophagy by inducing LC3 lipidation autophagosome formation which abolished inhibitor 3-methyladenine. Further study showed displayed no effects on PI3KC3 or Beclin 1 expression but downregulated enzymatic activity of mammalian target Rapamycin (mTOR), a critical modulator autophagy. Moreover, inhibited catalytic mTOR complex 1, thus suppressing phosphorylation P70S6K 4E-BP1, two major proteins associated with in mTORC1 signaling pathway. induced leukemia myeloma apoptosis, however, addition 3-methyladenine attenuated this kind Therefore, demonstrated that induces apoptosis cells disrupting

参考文章(29)
G Marino, Carlos López-Otín, Autophagy: molecular mechanisms, physiological functions and relevance in human pathology Cellular and Molecular Life Sciences. ,vol. 61, pp. 1439- 1454 ,(2004) , 10.1007/S00018-004-4012-4
Helena Pópulo, José Manuel Lopes, Paula Soares, The mTOR signalling pathway in human cancer. International Journal of Molecular Sciences. ,vol. 13, pp. 1886- 1918 ,(2012) , 10.3390/IJMS13021886
Xinliang Mao, A Keith Stewart, Rose Hurren, Alessandro Datti, Xuegong Zhu, Yuanxiao Zhu, Changxin Shi, Kyle Lee, Rodger Tiedemann, Yanina Eberhard, Suzanne Trudel, Shengben Liang, Seth J Corey, Lisa C Gillis, Dwayne L Barber, Jeffery L Wrana, Shereen Ezzat, Aaron D Schimmer, None, A chemical biology screen identifies glucocorticoids that regulate c-maf expression by increasing its proteasomal degradation through up-regulation of ubiquitin. Blood. ,vol. 110, pp. 4047- 4054 ,(2007) , 10.1182/BLOOD-2007-05-088666
Jeffrey A. Engelman, Targeting PI3K signalling in cancer: opportunities, challenges and limitations Nature Reviews Cancer. ,vol. 9, pp. 550- 562 ,(2009) , 10.1038/NRC2664
Yukiko Kabeya, Noboru Mizushima, Takashi Ueno, Akitsugu Yamamoto, Takayoshi Kirisako, Takeshi Noda, Eiki Kominami, Yoshinori Ohsumi, Tamotsu Yoshimori, LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing The EMBO Journal. ,vol. 19, pp. 5720- 5728 ,(2000) , 10.1093/EMBOJ/19.21.5720
Biyin Cao, Jie Li, Jingyu Zhu, Mingyun Shen, Kunkun Han, Zubin Zhang, Yang Yu, Yali Wang, Depei Wu, Suning Chen, Aining Sun, Xiaowen Tang, Yun Zhao, Chunhua Qiao, Tingjun Hou, Xinliang Mao, The antiparasitic clioquinol induces apoptosis in leukemia and myeloma cells by inhibiting histone deacetylase activity. Journal of Biological Chemistry. ,vol. 288, pp. 34181- 34189 ,(2013) , 10.1074/JBC.M113.472563
Chang Hwa Jung, Seung-Hyun Ro, Jing Cao, Neil Michael Otto, Do-Hyung Kim, mTOR regulation of autophagy FEBS Letters. ,vol. 584, pp. 1287- 1295 ,(2010) , 10.1016/J.FEBSLET.2010.01.017
Viktor I. Korolchuk, David C. Rubinsztein, Regulation of autophagy by lysosomal positioning. Autophagy. ,vol. 7, pp. 927- 928 ,(2011) , 10.4161/AUTO.7.8.15862
Zi-yue Li, Yu Yang, Miao Ming, Bo Liu, Mitochondrial ROS generation for regulation of autophagic pathways in cancer. Biochemical and Biophysical Research Communications. ,vol. 414, pp. 5- 8 ,(2011) , 10.1016/J.BBRC.2011.09.046
Takahiro Shintani, Daniel J Klionsky, Autophagy in Health and Disease: A Double-Edged Sword Science. ,vol. 306, pp. 990- 995 ,(2004) , 10.1126/SCIENCE.1099993