title: Apigenin decreases cell viability and telomerase activity in human leukemia cell lines.
abstract: Recent studies have shown that apigenin (4',5,7-trihydroxyflavone inhibits human malignant cancer cell growth through cell cycle arrest and apoptosis. However, the underlying relationship between apoptosis and telomerase activity in response to apigenin exposure is not well understood. In this study, we found that apigenin significantly induces direct cytotoxicity in human leukemia cells (U937, THP-1 and HL60) through activation of the caspase pathway. As we presumed, treatment with apigenin was found to increase the level of intracellular reactive oxygen species (ROS), whereas pretreatment with antioxidants, N-acetyl-cysteine (NAC) or glutathione (GSH), completely attenuated ROS generation. Surprisingly, these antioxidants did not promote recuperation from apigenin-induced cell death. We further showed that apigenin downregulates telomerase activity in caspase-dependent apoptosis and observed that apigenin dosing results in downregulation of telomerase activity by suppression of c-Myc-mediated telomerase reverse transcriptase (hTERT) expression. In addition, treatment of apigenin-dosed cells with the two antioxidants did not restore telomerase activity. Taken together, this data suggests that ROS is not essential for suppression of apigenin-mediated apoptosis associated with the activation of caspases and regulation of telomerase activity via suppression of hTERT. We conclude that apigenin has a direct cytotoxic effect and the loss of telomerase activity in leukemia cells.
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: R G P T
authors.initials: RG
authors.lastname: Jayasooriya
authors.forename: Sang-Hyuck
authors.initials: SH
authors.lastname: Kang
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Kang
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Dong-Oh
authors.initials: DO
authors.lastname: Moon
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Hyun
authors.forename: Weon-Young
authors.initials: WY
authors.lastname: Chang
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D017382:Reactive Oxygen Species; D047310:Apigenin; D019098:Telomerase; D005978:Glutathione; D000111:Acetylcysteine