Anticancer Agents Med Chem. 2013 Sep;13(7):1088-95.

Suppression of oncoprotein Her-2 and DNA damage after treatment with Flavan-3- ol vitis labrusca extract.

Scola G, Fernandes Correia Laurino CC, Menin E, Salvador M.

Institute of Biotechnology, University of Caxias do Sul, 1130 Getulio Vargas St., Caxias do Sul, RS 95070560, Brazil.

 

Abstract

Hepatocellular carcinoma and breast cancer are the most prevalent cancers in the world with high morbidity and mortality. Although there are effective drugs for treating advanced stages of liver and breast cancers, the prognosis for patients with liver cancer remains poor, and patients with breast cancer show considerable mortality. Therefore, it is crucial to explore new therapeutic agents for the inhibition of carcinogenesis. This study examined the anti-carcinogenic effect of Vitis labrusca seed extract (VLE), which is a component of winery waste, on liver (HepG2) and breast cancers (MCF-7) cells. The results found in this study demonstrated VLEinduced DNA damage in liver and breast cancer cells. VLE treatment in both cell lines was accompanied by high NO production and upregulation of p53. A significant decrease in total PARP expression was also found in HepG2 cells. In the MCF-7 cell line, VLE treatment increased the expression of Bax and AIF, and decreased total PARP expression. Surprisingly, VLE suppressed Her-2 expression in HepG2 cells and caused a subtle, but significant downregulation of Her-2 in MCF-7 cells. The possible anti-carcinogenic effect of VLE reported in this study suggests the potential of this extract to be used for the development of novel therapeutic agents for the treatment of different kinds of cancers.

PMID: 23343084

 

SUPPLEMENT:

While there are effective drugs for treating advanced stages of liver and breast cancers, these cancers remain one of the leading causes of death. Therefore, it is crucial to explore new therapeutic agents, to be used independently or in combination, for the inhibition of carcinogenesis that potentially have similar biological effects as chemotherapeutics without the negative consequences. In this study, an extract made from the seeds of Vitis labrusca obtained from winery wastes was used to assess its effectiveness against liver (HepG2) and breast cancer (MCF-7) cells.

Research has shown that extracts from grape seeds are safe for human consumption. Furthermore, grape seed extract has been linked to cancer prevention/therapy and exhibits cytotoxicity to cancer cells but not to normal cells. In addition, several studies were reported using different extracts from grapes or grape seeds showing that grape polyphenols could be used in standard chemotherapeutic regimens for various forms of cancers. In this study, the Vitis labrusca extract (VLE) produced significant changes in HepG2 and MCF-7 cells, which included growth inhibition (<1mg/mL), cytotoxic effects (>1mg/mL), induction of markers of DNA damage, alterations in cell signaling pathways, and downregulation of Her-2 and total PARP expression.

The findings of this study suggest that VLE presented an anti-carcinogenic effect that can be attributed to the induction of DNA damage and cell death. VLE induced an increase on nitric oxide production, leading to oxidative DNA breakage. On HepG2 cells, VLE stimulated an increase in p53 levels, which downregulated total PARP. In MCF-7, p53 activated Bax, which released AIF, and downregulated total PARP. Importantly, VLE caused suppression of the oncoprotein, Her-2, in HepG2 and MCF-7 cells. Taken together, these results suggest that VLE regulates important anti-carcinogenic pathways that synergistically could induce liver and breast cancer cell death. This demonstrates the potential of the compounds present in winery wastes seeds to be developed as therapeutic agents against different types of cancers.

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