4-Amino-3-acetylquinoline-induced apoptosis of murine L1210 leukemia cells involves ROS-mitochondrial-mediated death signaling and activation of p38 MAPK.
Quinolines are known to be multitarget agents with a broad spectrum of biological activity. In a previous study, we showed that newly prepared 4-amino-3-acetylquinoline (AAQ) possesses strong anticancer activities. In this study, we investigated whether AAQ has cytotoxicity in murine L1210 leukemia cells. Results from cell proliferation assays showed that AAQ caused significant decrease in cell number in a dose-dependent manner. The cell death induced by AAQ appeared to involve apoptosis, based on evidence from apoptotic DNA fragmentation, flow cytometry, fluorescence microscopy, and Western blot analyses. We found that AAQ-treated cells had activated p38 MAPK and that apoptosis was processed through a reactive oxygen species (ROS)-dependent mitochondrial pathway. In summary, our results suggest that AAQ can induce apoptosis, at least in part, through the activation of the p38 MAPK pathway in L1210 leukemia cells.
Jantová
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Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, Slovakia. sona.jantova@stuba.sk
Repický
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Letasiová
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Cipák
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D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006131:Growth Inhibitors / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D011804:Quinolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C522284:4-amino-3-acetylquinoline; D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D011804:Quinolines; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases