Curcumin-induced cell cycle arrest and apoptosis in human acute promyelocytic leukemia HL-60 cells via MMP changes and caspase-3 activation.
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.
Tan
Tzu-Wei
TW
Department of Pharmacology, China Medical University, Taichung 404, ROC.
Tsai
Hsin-Ru
HR
Lu
Hsu-Feng
HF
Lin
Hui-Lu
HL
Tsou
Mei-Fen
MF
Lin
Yuh-Tzy
YT
Tsai
Huei-Yann
HY
Chen
Yuh-Fung
YF
Chung
Jing-Gung
JG
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
D017382:Reactive Oxygen Species; D053148:Caspase 3; D020782:Matrix Metalloproteinases; D003474:Curcumin