| Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin. | |
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MedLine Citation:
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PMID: 19172579 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1-4 linkages containing between 2-8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79-479 microg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 microg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 microg/ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells. |
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Authors:
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Ajay P Singh; Rakesh K Singh; Kyu Kwang Kim; K S Satyan; Roger Nussbaum; Monica Torres; Laurent Brard; Nicholi Vorsa |
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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: Phytotherapy research : PTR Volume: 23 ISSN: 1099-1573 ISO Abbreviation: Phytother Res Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-03 Completed Date: 2009-09-23 Revised Date: 2010-09-22 |
Medline Journal Info:
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Nlm Unique ID: 8904486 Medline TA: Phytother Res Country: England |
Other Details:
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Languages: eng Pagination: 1066-74 Citation Subset: IM |
Copyright Information:
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Copyright 2009 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Plant Biology and Plant Pathology, Rutgers University, New Brunswick, NJ 08019, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects Carboplatin / pharmacology* Cell Line, Tumor Cell Proliferation / drug effects Female Flavonoids / isolation & purification, pharmacology Humans Ovarian Neoplasms / drug therapy Phenols / isolation & purification, pharmacology Plant Extracts / pharmacology* Proanthocyanidins / isolation & purification, pharmacology* Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Vaccinium macrocarpon / chemistry* |
| Grant Support | |
ID/Acronym/Agency:
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5R01AT002058/AT/NCCAM NIH HHS; K12 HD043447/HD/NICHD NIH HHS; K12 HD043447-05/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Flavonoids; 0/Phenols; 0/Plant Extracts; 0/Proanthocyanidins; 0/polyphenols; 41575-94-4/Carboplatin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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