NDLI: Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols

Content Provider	Springer Nature Link
Author	Castillo Pichardo, Linette Martínez Montemayor, Michelle M. Martínez, Joel E. Wall, Kristin M. Cuba, Luis A. Dharmawardhane, Suranganie
Copyright Year	2009
Abstract	The cancer preventive properties of grape products such as red wine have been attributed to polyphenols enriched in red wine. However, much of the studies on cancer preventive mechanisms of grape polyphenols have been conducted with individual compounds at concentrations too high to be achieved via dietary consumption. We recently reported that combined grape polyphenols at physiologically relevant concentrations are more effective than individual compounds at inhibition of ERα(−), ERβ(+) MDA-MB-231 breast cancer cell proliferation, cell cycle progression, and primary mammary tumor growth (Schlachterman et al., Transl Oncol 1:19–27, 2008). Herein, we show that combined grape polyphenols induce apoptosis and are more effective than individual resveratrol, quercetin, or catechin at inhibition of cell proliferation, cell cycle progression, and cell migration in the highly metastatic ER (−) MDA-MB-435 cell line. The combined effect of dietary grape polyphenols (5 mg/kg each resveratrol, quercetin, and catechin) was tested on progression of mammary tumors in nude mice created from green fluorescent protein-tagged MDA-MB-435 bone metastatic variant. Fluorescence image analysis of primary tumor growth demonstrated a statistically significant decrease in tumor area by dietary grape polyphenols. Molecular analysis of excised tumors demonstrated that reduced mammary tumor growth may be due to upregulation of FOXO1 (forkhead box O1) and NFKBIA (IκBα), thus activating apoptosis and potentially inhibiting NfκB (nuclear factor κB) activity. Image analysis of distant organs for metastases demonstrated that grape polyphenols reduced metastasis especially to liver and bone. Overall, these results indicate that combined dietary grape polyphenols are effective at inhibition of mammary tumor growth and site-specific metastasis.
Starting Page	505
Ending Page	516
Page Count	12
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	26
Issue Number	6
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-03-18
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Breast cancer Catechin Metastasis Quercetin Resveratrol Surgical Oncology Hematology Oncology Biomedicine general Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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