| Ircinin-1 induces cell cycle arrest and apoptosis in SK-MEL-2 human melanoma cells. | |
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MedLine Citation:
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PMID: 16163705 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated the effects of ircinin-1, a lipid compound (a C25 sesterterpene tetronic acid) isolated from marine sponges (Sarcotragus sp.), on the modulation of cell cycle and induction of apoptosis in SK-MEL-2 human skin cancer cells (mutant p53). Ircinin-1 treatment on SK-MEL-2 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death. Flow cytometric analysis revealed that ircinin-1 resulted in G1 arrest in cell cycle progression which was associated with a marked decrease in the protein expression of D-type cyclins and their activating partners Cdk 4 and 6 with concomitant inductions of p21WAF1/CIP1 and p27KIP1. The induction of p21WAF1/CIP1 appears to be transcriptionally upregulated and is p53-independent. In addition, ircinin-1 suppressed the phosphorylation of pRb protein and increased the co-association of pRb or proliferating cell nuclear antigen (PCNA) with p21WAF1/CIP1 in these cells. Ircinin-1 treatment also resulted in induction of apoptosis as determined by morphological changes, DNA fragmentation, alternated ratio of Bax/Bcl-2, cleavages of poly(ADP-ribose) polymerase and PLC-gamma1, and flow cytometric analysis. Ircinin-1 also induced cytochrome c release, cleavage activations of caspase-3 and -9, and upregulation of Fas and Fas-L. Even though the inhibitor of apoptosis protein (IAP) was expressed in ircinin-1-untreated or -treated SK-MEL-2 cells, only the level of cIAP-1, but not XIAP or cIAP-2, was decreased during ircinin-1-induced apoptosis at Western blot and RT-PCR studies. Taken together, these findings suggest that ircinin-1 has strong potential for development as an agent for prevention against skin cancer. |
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Authors:
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Hye Joung Choi; Yung Hyun Choi; Su-Bog Yee; Eunok Im; Jee Hyung Jung; Nam Deuk Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular carcinogenesis Volume: 44 ISSN: 0899-1987 ISO Abbreviation: Mol. Carcinog. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-10-17 Completed Date: 2005-12-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8811105 Medline TA: Mol Carcinog Country: United States |
Other Details:
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Languages: eng Pagination: 162-73 Citation Subset: IM |
Copyright Information:
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Copyright 2005 Wiley-Liss, Inc |
Affiliation:
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Department of Pharmacy and Pusan Cancer Research Center, Pusan National University, Busan, South Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Caspases / metabolism Cell Cycle / drug effects* Cell Cycle Proteins / genetics, metabolism Cell Line, Tumor DNA / metabolism Down-Regulation E2F1 Transcription Factor / metabolism Fas Ligand Protein Furans / chemistry, pharmacology* Humans Inhibitor of Apoptosis Proteins / metabolism Melanoma / genetics, metabolism, pathology* Membrane Glycoproteins / metabolism Molecular Structure Phosphorylation Proliferating Cell Nuclear Antigen / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Retinoblastoma Protein / metabolism Sesquiterpenes / chemistry, pharmacology* Tumor Necrosis Factors / metabolism Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Cell Cycle Proteins; 0/E2F1 Transcription Factor; 0/E2F1 protein, human; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Furans; 0/Inhibitor of Apoptosis Proteins; 0/Membrane Glycoproteins; 0/Proliferating Cell Nuclear Antigen; 0/Proto-Oncogene Proteins c-bcl-2; 0/Retinoblastoma Protein; 0/Sesquiterpenes; 0/Tumor Necrosis Factors; 0/ircinin-1; 9007-49-2/DNA; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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