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Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways.
J Cell Biochem 2010; 111(3):742-54JC

Abstract

Prostate cancer is one of the most common cancers in the Western world, and it is believed that an individual's diet affects his risk of developing cancer. There has been an interest in examining phytochemicals, the secondary metabolites of plants, in order to determine their potential anti-cancer activities in vitro and in vivo. In this study we document the effects of proanthocyanidins (PACs) from the American Cranberry (Vaccinium macrocarpon) on matrix metalloproteinase (MMP) activity in DU145 human prostate cancer cells. Cranberry PACs decreased cellular viability of DU145 cells at a concentration of 25 µg/ml by 30% after 6 h of treatment. Treatment of DU145 cells with PACs resulted in an inhibition of both MMPs 2 and 9 activity. PACs increased the expression of TIMP-2, a known inhibitor of MMP activity, and decreased the expression of EMMPRIN, an inducer of MMP expression. PACs decreased the expression of PI-3 kinase and AKT proteins, and increased the phosphorylation of both p38 and ERK1/2. Cranberry PACs also decreased the translocation of the NF-κB p65 protein to the nucleus. Cranberry PACs increased c-jun and decreased c-fos protein levels. These results suggest that cranberry PACs decreases MMP activity through the induction and/or inhibition of specific temporal MMP regulators, and by affecting either the phosphorylation status and/or expression of MAP kinase, PI-3 kinase, NF-κB and AP-1 pathway proteins. This study further demonstrates that cranberry PACs are a strong candidate for further research as novel anti-cancer agents.

Authors+Show Affiliations

Department of Biology, University of Prince Edward Island, Prince Edward Island, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20626034

Citation

Déziel, Bob A., et al. "Proanthocyanidins From the American Cranberry (Vaccinium Macrocarpon) Inhibit Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Activity in Human Prostate Cancer Cells Via Alterations in Multiple Cellular Signalling Pathways." Journal of Cellular Biochemistry, vol. 111, no. 3, 2010, pp. 742-54.
Déziel BA, Patel K, Neto C, et al. Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways. J Cell Biochem. 2010;111(3):742-54.
Déziel, B. A., Patel, K., Neto, C., Gottschall-Pass, K., & Hurta, R. A. (2010). Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways. Journal of Cellular Biochemistry, 111(3), pp. 742-54. doi:10.1002/jcb.22761.
Déziel BA, et al. Proanthocyanidins From the American Cranberry (Vaccinium Macrocarpon) Inhibit Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Activity in Human Prostate Cancer Cells Via Alterations in Multiple Cellular Signalling Pathways. J Cell Biochem. 2010 Oct 15;111(3):742-54. PubMed PMID: 20626034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proanthocyanidins from the American Cranberry (Vaccinium macrocarpon) inhibit matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in human prostate cancer cells via alterations in multiple cellular signalling pathways. AU - Déziel,Bob A, AU - Patel,Kunal, AU - Neto,Catherine, AU - Gottschall-Pass,Katherine, AU - Hurta,Robert A R, PY - 2010/7/14/entrez PY - 2010/7/14/pubmed PY - 2011/2/1/medline SP - 742 EP - 54 JF - Journal of cellular biochemistry JO - J. Cell. Biochem. VL - 111 IS - 3 N2 - Prostate cancer is one of the most common cancers in the Western world, and it is believed that an individual's diet affects his risk of developing cancer. There has been an interest in examining phytochemicals, the secondary metabolites of plants, in order to determine their potential anti-cancer activities in vitro and in vivo. In this study we document the effects of proanthocyanidins (PACs) from the American Cranberry (Vaccinium macrocarpon) on matrix metalloproteinase (MMP) activity in DU145 human prostate cancer cells. Cranberry PACs decreased cellular viability of DU145 cells at a concentration of 25 µg/ml by 30% after 6 h of treatment. Treatment of DU145 cells with PACs resulted in an inhibition of both MMPs 2 and 9 activity. PACs increased the expression of TIMP-2, a known inhibitor of MMP activity, and decreased the expression of EMMPRIN, an inducer of MMP expression. PACs decreased the expression of PI-3 kinase and AKT proteins, and increased the phosphorylation of both p38 and ERK1/2. Cranberry PACs also decreased the translocation of the NF-κB p65 protein to the nucleus. Cranberry PACs increased c-jun and decreased c-fos protein levels. These results suggest that cranberry PACs decreases MMP activity through the induction and/or inhibition of specific temporal MMP regulators, and by affecting either the phosphorylation status and/or expression of MAP kinase, PI-3 kinase, NF-κB and AP-1 pathway proteins. This study further demonstrates that cranberry PACs are a strong candidate for further research as novel anti-cancer agents. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/20626034/Proanthocyanidins_from_the_American_Cranberry__Vaccinium_macrocarpon__inhibit_matrix_metalloproteinase_2_and_matrix_metalloproteinase_9_activity_in_human_prostate_cancer_cells_via_alterations_in_multiple_cellular_signalling_pathways_ L2 - https://doi.org/10.1002/jcb.22761 DB - PRIME DP - Unbound Medicine ER -