Document Detail


Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin.
MedLine Citation:
PMID:  19172579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Phytotherapy research : PTR     Volume:  23     ISSN:  1099-1573     ISO Abbreviation:  Phytother Res     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-03     Completed Date:  2009-09-23     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  8904486     Medline TA:  Phytother Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1066-74     Citation Subset:  IM    
Copyright Information:
Copyright 2009 John Wiley & Sons, Ltd.
Affiliation:
Department of Plant Biology and Plant Pathology, Rutgers University, New Brunswick, NJ 08019, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / 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*
Polyphenols
Proanthocyanidins / isolation & purification,  pharmacology*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Vaccinium macrocarpon / chemistry*
Grant Support
ID/Acronym/Agency:
5R01AT002058/AT/NCCAM NIH HHS; K12 HD043447/HD/NICHD NIH HHS; K12 HD043447-05/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Flavonoids; 0/Phenols; 0/Plant Extracts; 0/Polyphenols; 0/Proanthocyanidins; 41575-94-4/Carboplatin
Comments/Corrections

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