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Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin.
Phytother Res. 2009 Aug; 23(8):1066-74.PR

Abstract

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+Show Affiliations

Department of Plant Biology and Plant Pathology, Rutgers University, New Brunswick, NJ 08019, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19172579

Citation

Singh, Ajay P., et al. "Cranberry Proanthocyanidins Are Cytotoxic to Human Cancer Cells and Sensitize Platinum-resistant Ovarian Cancer Cells to Paraplatin." Phytotherapy Research : PTR, vol. 23, no. 8, 2009, pp. 1066-74.
Singh AP, Singh RK, Kim KK, et al. Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin. Phytother Res. 2009;23(8):1066-74.
Singh, A. P., Singh, R. K., Kim, K. K., Satyan, K. S., Nussbaum, R., Torres, M., Brard, L., & Vorsa, N. (2009). Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin. Phytotherapy Research : PTR, 23(8), 1066-74. https://doi.org/10.1002/ptr.2667
Singh AP, et al. Cranberry Proanthocyanidins Are Cytotoxic to Human Cancer Cells and Sensitize Platinum-resistant Ovarian Cancer Cells to Paraplatin. Phytother Res. 2009;23(8):1066-74. PubMed PMID: 19172579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cranberry proanthocyanidins are cytotoxic to human cancer cells and sensitize platinum-resistant ovarian cancer cells to paraplatin. AU - Singh,Ajay P, AU - Singh,Rakesh K, AU - Kim,Kyu Kwang, AU - Satyan,K S, AU - Nussbaum,Roger, AU - Torres,Monica, AU - Brard,Laurent, AU - Vorsa,Nicholi, PY - 2009/1/28/entrez PY - 2009/1/28/pubmed PY - 2009/9/24/medline SP - 1066 EP - 74 JF - Phytotherapy research : PTR JO - Phytother Res VL - 23 IS - 8 N2 - 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. SN - 1099-1573 UR - https://www.unboundmedicine.com/medline/citation/19172579/Cranberry_proanthocyanidins_are_cytotoxic_to_human_cancer_cells_and_sensitize_platinum_resistant_ovarian_cancer_cells_to_paraplatin_ L2 - https://doi.org/10.1002/ptr.2667 DB - PRIME DP - Unbound Medicine ER -