Quercetin simultaneously induces G0/G1-phase arrest and caspase-mediated crosstalk between apoptosis and autophagy in human leukemia HL-60 cells

Junn Liang Chang, Jyh Ming Chow, Jer Hwa Chang, Yu-Ching Wen, Yung Wei Lin, Shun Fa Yang, Wei Jiunn Lee, Ming Hsien Chien

研究成果: 雜誌貢獻文章

12 引文 斯高帕斯(Scopus)

摘要

Quercetin is a plant-derived bioflavonoid with high anticancer activity in various tumors. Herein, the molecular mechanisms by which quercetin exerts its anticancer effects against HL-60 acute myeloid leukemia (AML) cells were investigated. Results showed that quercetin suppressed cell proliferation in the HL-60 cell line in vitro and in vivo. Quercetin-induced G0/G1-phase arrest occurred when expressions of cyclin-dependent kinase (CDK)2/4 were inhibited and the CDK inhibitors, p16 and p21, were induced. Moreover, quercetin treatment not only activated proapoptotic signaling like poly (ADP ribose) polymerase (PARP)-1 cleavage and caspase activation but also triggered autophagy events as shown by the increased expression of light chain 3 (LC3)-II, decreased expression of p62, and formation of acidic vesicular organelles. Interestingly, it was found that use of the autophagy inhibitor, 3-methyladenine, significantly enhanced quercetin-mediated apoptotic cell death as analyzed by MTS and DNA fragmentation assays. Moreover, pretreatment of HL-60 cells with the pan-caspase inhibitor, Z-VAD-fmk, dramatically reversed quercetin-mediated apoptotic and autophagic cell death. Although apoptosis and autophagy are two independent cell death pathways, our findings indicated that quercetin can activate caspases to trigger these two pathways, and both pathways played contrary roles in quercetin-mediated HL-60 cell death. In conclusion, besides promoting apoptosis, quercetin also induced cytoprotective autophagy in HL-60 cells, and inhibition of autophagy may be a novel strategy to enhance the anticancer activity of quercetin in AML.
原文英語
期刊Environmental Toxicology
DOIs
出版狀態接受/付印 - 2017

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

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