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Title of article :
Petrotetrayndiol A induces cell cycle arrest and apoptosis in SK-MEL-2 human melanoma cells through cytochrome c-mediated activation of caspases
Author/Authors :
Choi، نويسنده , , Hye Joung and Yee، نويسنده , , Su-Bog and Park، نويسنده , , Sang Eun and Im، نويسنده , , Eunok and Jung، نويسنده , , Jee Hyung and Chung، نويسنده , , Hae Young and Choi، نويسنده , , Yung Hyun and Kim، نويسنده , , Nam Deuk Kim، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2006
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Abstract :
We investigated the possible mechanisms by which petrotetrayndiol A, a polyacetylene from the sponge Petrosia sp., exerts its anti-proliferative activity in cultured SK-MEL-2 human melanoma cells. Petrotetrayndiol A-treated SK-MEL-2 cells showed growth inhibition and induction of apoptosis in a dose-dependent manner as measured by MTT assay, fluorescent microscopy and flow cytometric analysis. Flow cytometric analysis revealed that petrotetrayndiol A resulted in G2/M arrest in the cell cycle progression which was associated with a marked decrease in the protein expression of cyclin B1 and its activating partner Cdc2 with concomitant inductions of p21WAF1/CIP1. The increase in apoptosis was associated with a dose-dependent up-regulation of cytosolic factor, such as Bax and release of cytochrome c, and down-regulation of Bcl-2. We also observed activation of caspase-9 and caspase-3, DNA ladder formation, proteolytic degradation of poly(ADP-ribose)-polymerase (PARP), and selective down-regulation of cIAP-1. The apoptotic manifestations, such as PARP cleavage and DNA fragmentation, were abolished in the presence of the tripeptide caspase inhibitor z-VAD-fmk and a caspase-3-specific inhibitor Ac-DEVD-cho. Our data thus demonstrate that petrotetrayndiol A-induced apoptosis and growth inhibition of SK-MEL-2 cells is dependent on caspase activation.
Keywords :
Petrotetrayndiol A , G2/M arrest , Polyacetylene , apoptosis , caspase , cytochrome c
Journal title :
Cancer Letters
Journal title :
Cancer Letters
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