| Petrotetrayndiol A induces cell cycle arrest and apoptosis in SK-MEL-2 human melanoma cells through cytochrome c-mediated activation of caspases. | |
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MedLine Citation:
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PMID: 16458118 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hye Joung Choi; Su-Bog Yee; Sang Eun Park; Eunok Im; Jee Hyung Jung; Hae Young Chung; Yung Hyun Choi; Nam Deuk Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-04-26 |
Journal Detail:
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Title: Cancer letters Volume: 232 ISSN: 0304-3835 ISO Abbreviation: Cancer Lett. Publication Date: 2006 Feb |
Date Detail:
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Created Date: 2006-02-06 Completed Date: 2006-04-06 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 214-25 Citation Subset: IM |
Affiliation:
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Department of Pharmacy and Pusan Cancer Research Center, Pusan National University, Busan 609-735, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylene
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analogs & derivatives*,
pharmacology Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects* Caspases / physiology* Cell Cycle / drug effects* Cell Line, Tumor Cyclin-Dependent Kinase Inhibitor p21 / physiology Cytochromes c / physiology* Enzyme Activation Humans Inhibitor of Apoptosis Proteins / antagonists & inhibitors Melanoma / drug therapy*, pathology Polyacetylenes Porifera / chemistry* Proto-Oncogene Proteins c-bcl-2 / analysis |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Inhibitor of Apoptosis Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/petrotetrayndiol A; 25067-58-7/Polyacetylenes; 74-86-2/Acetylene; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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