Investigation of anticancer mechanism of clavulone II, a coral cyclopentenone prostaglandin analog, in human acute promyelocytic leukemia
Journal
Journal of Biomedical Science
Journal Volume
12
Journal Issue
2
Pages
335-345
Date Issued
2005
Author(s)
Abstract
The marine prostanoid clavulones were shown to exert cytotoxicity against several cancer cells. In the present study, we illustrate the pathways utilized by clavulone II to trigger apoptotic signaling in human acute promyelocytic leukemia HL-60 cells. Exposure of cells to clavulone II resulted in early induction of phosphatidylserine externalization, mitochondrial dysfunction, and alteration of the cell cycle. Down-regulated expression of cyclin D1 explained the effect of clavulone II on G1 phase arrest of the cell cycle. Clavulone II induced the disruption of mitochondrial membrane potential and activation of caspase-8, -9 and -3 in a time- and concentration-dependent manner. Furthermore, the effect of 3 μM clavulone II was accompanied by the up-regulation of Bax, down-regulation of Mcl-1, and cleavage of Bid. Taken together, it is suggested that low concentrations of clavulone II induce the antiproliferative effect through the down-regulation of cyclin D1 expression and G1 arrest of the cell cycle, while that of high concentration induce the apoptotic cell death via the modulation of members of caspases and Bcl-2 family proteins in HL-60 cells. ? 2005 National Science Council.
Other Subjects
antineoplastic agent; caspase 3; caspase 8; caspase 9; claviridenone c; clavulone derivative; cyclin D1; cyclopentenone derivative; prostaglandin derivative; protein Bax; protein bcl 2; protein Bid; unclassified drug; antineoplastic activity; apoptosis; article; cell cycle; cell cycle G1 phase; cell death; cell proliferation; cell strain HL 60; concentration response; controlled study; down regulation; drug exposure; enzyme activation; human; human cell; membrane potential; mitochondrial membrane; priority journal; promyelocytic leukemia; protein degradation; protein expression; protein induction; signal transduction; upregulation; Animals; Anthozoa; Antineoplastic Agents; Apoptosis; Blotting, Western; Caspase 3; Caspase 8; Caspase 9; Caspases; Cell Cycle; Cell Proliferation; Cell Separation; Cyclin D1; DNA; Dose-Response Relationship, Drug; Down-Regulation; Flow Cytometry; G1 Phase; HL-60 Cells; Humans; Inhibitory Concentration 50; Intracellular Membranes; Leukemia, Promyelocytic, Acute; Membrane Potentials; Models, Chemical; Oxidation-Reduction; Oxidative Stress; Prostaglandins; Prostaglandins A; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Time Factors; Anthozoa
Type
journal article