title: Curcumin-induced cell cycle arrest and apoptosis in human acute promyelocytic leukemia HL-60 cells via MMP changes and caspase-3 activation.
abstract: Curcumin (diferuloylmethane), is a natural product derived from the root of the plant Curcuma longa. For centuries, it has been used as a spice and as a herbal medicine in Chinese populations. Curcumin has been shown to inhibit cell proliferation, cell cycle arrest, cyclooxygenase (COX)-1 and -2 expression and apoptosis in several human cancer cell lines. The aim of this investigation was to clarify the mechanisms by which curcumin induced cytotoxicity and apoptosis in human leukemia HL-60 cells. The effects of curcumin on the levels of reactive oxygen species (ROS), Ca+2 production, cyclin E, cdc25c, wee1, Bcl-2, Bax, the changes of mitochondrial membrane potential (MMP), cytochrome c release and the activation of caspase-3 were also investigated in the HL-60 cells. Results of flow cytometry and DAPI staining assays indicated that curcumin induced cytotoxicity and apoptosis in the examined cells. The results from flow cytometry assay indicated that curcumin induced ROS and Ca+2 productions, decreased the levels of MMP and increased the activity of caspase-3, leading to cell apoptosis. Western blot assay also revealed that curcumin increased the levels of Bax and the release of cytochrome c, and decreased the levels of Bcl-2 in the examined cells. The inhibition of caspase-3 activation by z-VAD-fmk (broad-spectrum caspase inhibitor) completely blocked curcumin-induced apoptosis in HL-60 cells.
authors.affiliation: Department of Pharmacology, China Medical University, Taichung 404, ROC.
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Tan
authors.forename: Hsin-Ru
authors.initials: HR
authors.lastname: Tsai
authors.forename: Hsu-Feng
authors.initials: HF
authors.lastname: Lu
authors.forename: Hui-Lu
authors.initials: HL
authors.lastname: Lin
authors.forename: Mei-Fen
authors.initials: MF
authors.lastname: Tsou
authors.forename: Yuh-Tzy
authors.initials: YT
authors.lastname: Lin
authors.forename: Huei-Yann
authors.initials: HY
authors.lastname: Tsai
authors.forename: Yuh-Fung
authors.initials: YF
authors.lastname: Chen
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D053148:Caspase 3; D020782:Matrix Metalloproteinases; D003474:Curcumin