TY - JOUR T1 - Gallic Acid Induces G<sub>0</sub>/G<sub>1</sub> Phase Arrest and Apoptosis in Human Leukemia HL-60 Cells through Inhibiting Cyclin D and E, and Activating Mitochondria-dependent Pathway JF - Anticancer Research JO - Anticancer Res SP - 2821 LP - 2832 VL - 31 IS - 9 AU - RU-DUAN YEH AU - JUNG-CHOU CHEN AU - TUNG-YUAN LAI AU - JAI-SING YANG AU - CHUN-SHU YU AU - JO-HUA CHIANG AU - CHI-CHENG LU AU - SU-TSO YANG AU - CHIEN-CHIH YU AU - SHU-JEN CHANG AU - HUI-YI LIN AU - JING-GUNG CHUNG Y1 - 2011/09/01 UR - http://ar.iiarjournals.org/content/31/9/2821.abstract N2 - 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 G0/G1 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 Ca2+ levels and reduced the mitochondrial membrane potential (ΔΨm) 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. ER -