Dfiq, a novel quinoline derivative, shows anticancer potential by inducing apoptosis and autophagy in nsclc cell and in vivo zebrafish xenograft models

Hurng Wern Huang, Yung Ding Bow, Chia Yih Wang, Yen Chun Chen, Pei Rong Fu, Kuo Feng Chang, Tso Wen Wang, Chih Hua Tseng, Yeh Long Chen, Chien Chih Chiu

研究成果: Article

摘要

Lung cancer is one of the deadliest cancers worldwide due to chemoresistance in patients with late-stage disease. Quinoline derivatives show biological activity against HIV, malaria, bacteriuria, and cancer. DFIQ is a novel synthetic quinoline derivative that induces cell death in both in vitro and in vivo zebrafish xenograft models. DFIQ induced cell death, including apoptosis, and the IC50 values were 4.16 and 2.31 μM at 24 and 48 h, respectively. DFIQ was also found to induce apoptotic protein cleavage and DNA damage, reduce cell cycle-associated protein expression, and disrupt reactive oxygen species (ROS) reduction, thus resulting in the accumulation of superoxide radicals. Autophagy is also a necessary process associated with chemotherapy-induced cell death. Lysosome accumulation and lysosome-associated membrane protein-2 (LAMP2) depletion were observed after DFIQ treatment, and cell death induction was restored upon treatment with the autophagy inhibitor 3-methyladenine (3-MA). Nevertheless, ROS production was found to be involved in DFIQ-induced autophagy activation and LAMP2 depletion. Our data provide the first evidence for developing DFIQ for clinical usage and show the regulatory mechanism by which DFIQ affects ROS, autophagy, and apoptosis.

原文English
文章編號1348
期刊Cancers
12
發行號5
DOIs
出版狀態Published - 2020 五月

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Huang, H. W., Bow, Y. D., Wang, C. Y., Chen, Y. C., Fu, P. R., Chang, K. F., Wang, T. W., Tseng, C. H., Chen, Y. L., & Chiu, C. C. (2020). Dfiq, a novel quinoline derivative, shows anticancer potential by inducing apoptosis and autophagy in nsclc cell and in vivo zebrafish xenograft models. Cancers, 12(5), [1348]. https://doi.org/10.3390/cancers12051348