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|標題:||Gallic Acid Induces G(0)/G(1) Phase Arrest and Apoptosis in Human Leukemia HL-60 Cells through Inhibiting Cyclin D and E, and Activating Mitochondria-dependent Pathway||作者:||Yeh, R.D.
|關鍵字:||Gallic acid (GA);human leukemia HL-60 cells;apoptosis;death;receptor-mediated pathways;mitochondria-mediated pathways;endoplasmic-reticulum stress;cancer-cells;triggers apoptosis;in-vitro;derivatives;death;phosphorylation;proliferation;antioxidant;induction||Project:||Anticancer Research||期刊/報告no：:||Anticancer Research, Volume 31, Issue 9, Page(s) 2821-2832.||摘要:||
Gallic acid (GA) induces apoptosis in different types of cancer cell lines. In this study, we investigate the apoptotic effects induced by GA in human promyelocytic leukemia HL-60 cells, and clarify the underlying mechanism. Our results showed that GA reduced the viability of HL-60 cells in a dose- and time-dependent manner. GA led to G(0)/G(1) phase arrest in HL-60 cells through promoting p21 and p27 and inhibiting the levels of cyclin D and cyclin E. GA caused DNA damage and fragmentation in HL-60 cells as assayed using DAPI staining and Comet assay. Flow cytometric analysis revealed that GA increased Ca(2+) levels and reduced the mitochondrial membrane potential (Delta Psi(m)) in HL-60 cells. Apoptotic protein expressions were determined by Western blotting. The results indicated that GA-mediated apoptosis of HL-60 cells mainly depended on mitochondrial pathway, by promoting the release of cytochrome c, apoptosis-inducing factor (AIF) and endonuclease G (Endo G) and by up-regulating the protein expression of Bcl-2-associated X protein (BAX), caspase-4, caspase-9 and caspase-3. In addition, GA also activated the death receptor-dependent pathway by enhancing the protein expressions of fatty acid synthase (FAS), FAS ligand (FASL), caspase-8 and BCL-2 interacting domain (BID). We determined the mRNA expression of the gene levels of these proteins by real-time PCR. The results showed that GA-mediated apoptosis of HL-60 cells mainly depended on up-regulation of the mRNA of caspase-8, caspase-9, caspase-3, AIF and Endo G. In conclusion, GA-induced apoptosis occurs through the death receptor and mitochondria-mediated pathways. The evaluation of GA as a potential therapeutic agent for treatment of leukemia seems warranted.
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