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• W3044136431 endingPage "1457" @default.
• W3044136431 startingPage "1445" @default.
• W3044136431 abstract "Abstract Objectives Acridone alkaloids from Citrus and their derivatives show various kinds of biological activity. However, the anticancer activities of dimeric acridone alkaloids with unique structures and the molecular mechanism of these effects are poorly understood. Methods We investigated the cytotoxicity effects of dimeric acridone alkaloids isolated from Marsh grapefruit on human myeloid leukaemia HL-60 cells. Key findings Of the six dimeric acridone alkaloids tested, citbismine-E, the most potent, dose- and time-dependently decreased HL-60 cell viability by inducing apoptosis. The treatment of HL-60 cells with citbismine-E yielded a significant increase in levels of intracellular reactive oxygen species (ROS). Citbismine-E lowered the mitochondrial membrane potential and increased the activities of caspase-9 and -3. In addition, citbismine-E-induced apoptosis, decrease in mitochondrial membrane potential and caspase activation were significantly alleviated by pretreatment of the cells with antioxidant N-acetylcysteine (NAC). Citbismine-E induced intrinsic caspase-dependent apoptosis through ROS-mediated c-Jun N-terminal kinase activation. Citbismine-E-induced production of oxidative stress biomarkers, malondialdehyde and 8-hydroxy-2′-deoxyguanosine was also attenuated by pretreatment with NAC. Conclusions Citbismine-E is a powerful cytotoxic agent against HL-60 cells that acts by inducing mitochondrial dysfunction-mediated apoptosis through ROS-dependent JNK activation. Citbismine-E also induced oxidative stress damage via ROS-mediated lipid peroxidation and DNA damage in HL-60 cells." @default.
• W3044136431 created "2020-07-29" @default.
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• W3044136431 date "2020-07-27" @default.
• W3044136431 modified "2023-10-13" @default.
• W3044136431 title "Cytotoxic activity of dimeric acridone alkaloids derived from Citrus plants towards human leukaemia HL-60 cells" @default.
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• W3044136431 doi "https://doi.org/10.1111/jphp.13327" @default.
• W3044136431 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32715490" @default.
• W3044136431 hasPublicationYear "2020" @default.
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