CA-5f is identified as a potent late-stage macroautophagy/autophagy inhibitor via inhibiting autophagosome-lysosome fusion. It exhibted potential clinical application for NSCLC therapy.
Macroautophagy/autophagy is a conserved eukaryotic cellular degradative process in which organelles and cellular proteins are sequestered in autophagosomes that subsequently fuse with lysosomes for further degradation and recycling. Autophagy plays essential roles in various normal cellular processes, including cell growth, proliferation, differentiation, development, ageing, and inflammation, to maintain cellular homeostasis [1]. CA-5f is a potent late-stage macroautophagy/autophagy inhibitor via inhibiting autophagosome-lysosome fusion, which CA-5f increases LC3B-II (a marker to monitor autophagy) and SQSTM1 protein, and also increases ROS production. CA-5f exhibited strong cytotoxicity against A549 non-small cell lung cancer (NSCLC) cells, but low cytotoxicity to normal human umbilical vein endothelial cells (HUVECs), by increasing mitochondrial-derived reactive oxygen species (ROS) production [1]. Moreover, CA-5f effectively suppressed the growth of A549 lung cancer xenograft as a single agent with an excellent tolerance in vivo[1].
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