| Mechanism of apoptosis with the involvement of calpain and caspase cascades in human malignant neuroblastoma SH-SY5Y cells exposed to flavonoids. | |
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MedLine Citation:
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PMID: 16988947 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neuroblastoma is the most common extracranial solid tumor in children causing death at pre-school age, as no cure has yet been developed. We investigated the proteolytic mechanisms for apoptosis in human malignant (N-type) neuroblastoma SH-SY5Y cells following exposure to flavonoids such as apigenin (APG), (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG) and genistein (GST). We found decrease in viability of SH-SY5Y cells with an increase in dose of APG, EGC, EGCG and GST. Predominantly apoptosis occurred following exposure of SH-SY5Y cells to 50 microM APG, 50 microM EGC, 50 microM EGCG and 100 microM GST for 24 hr. Apoptosis was associated with increases in intracellular free [Ca(2+)] and Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and activation of caspase-9, calpain and caspase-3. Induction of apoptosis with APG and GST showed activation of caspase-12 as well. Activation of caspase-3 could cleave the inhibitor-of-caspase-activated DNase (ICAD) to release and translocate caspase-3-activated DNase (CAD) to the nucleus. Activation of caspase-8 cleaved Bid to truncated Bid (tBid) in cells treated with EGC and EGCG. EGC and EGCG induced apoptosis with caspase-8 activation and mitochondria-mediated pathway, whereas APG and GST caused apoptosis via an increase in intracellular free [Ca(2+)] with calpain activation and mitochondria-mediated pathway. Activation of different proteases for cell death was confirmed using caspase-8 inhibitor II, calpeptin (calpain inhibitor), caspase-9 inhibitor I and caspase-3 inhibitor IV. Thus, plant-derived flavonoids cause cell death with activation of proteolytic activities of calpain and caspases in SH-SY5Y cells, and therefore serve as potential therapeutic agents for controlling the growth of neuroblastoma. |
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Authors:
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Arabinda Das; Naren L Banik; Swapan K Ray |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 119 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 2006 Dec |
Date Detail:
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Created Date: 2006-10-26 Completed Date: 2006-12-12 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 2575-85 Citation Subset: IM |
Affiliation:
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Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis* Calpain / physiology* Caspases / metabolism* Cell Line, Tumor Colorimetry Flavonoids / pharmacology* Humans Neuroblastoma / enzymology, metabolism, pathology* |
| Grant Support | |
ID/Acronym/Agency:
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CA-91460/CA/NCI NIH HHS; NS-31622/NS/NINDS NIH HHS; NS-57811/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Flavonoids; EC 3.4.22.-/Calpain; EC 3.4.22.-/Caspases |
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