Abstract
The pathophysiology of inflammation and oxidative stress generated during different types of cancers and anticancer treatments is well documented. Traditionally, grape pomace is used for animal feed, organic fertilizers, ethanol production or is disposed as waste. Because grape pomace is a rich source of antioxidant compounds, the purpose of the study was to evaluate the antioxidant, anti-inflammatory, and antiproliferative effects of fresh and fermented grape pomace extracts of two Vitis vinifera L. varieties Fetească neagră and Pinot noir cultivated in Romania. Firstly, grape pomace phytochemical analysis and in vitro antioxidant tests were performed. Secondly, the effect of a seven-day pretreatment with grape pomace extracts on the turpentine oil-induced inflammation in rats was assessed by measuring total oxidative status, total antioxidant response, oxidative stress index, malondialdehyde, total thiols, nitric oxide and 3-nitrotyrosine. Thirdly, the antiproliferative properties were evaluated on human lung carcinoma (A549), human breast adenocarcinoma (MDA-MB-231), murine melanoma (B164A5), and keratinocyte (HaCat) cell lines. Fetească neagră and Pinot noir grape pomace extracts have a rich content of polyphenols and in vitro antioxidant effect. Fermented samples had higher polyphenol content, but fresh samples had better antioxidant activity. Pretreatment with grape pomace extracts reduced inflammation-induced oxidative stress in a concentration-dependent way, fresh samples being more efficient. The malignant cells’ proliferation was inhibited by all grape pomace extracts, fermented Fetească neagră extracts having the strongest effect. Conclusion: fresh and fermented pomace extracts of Vitis vinifera L. varieties Fetească neagră and Pinot noir cultivated in a Romanian wine region have antioxidant, anti-inflammatory and antiproliferative effects.
Highlights
During tumor development tissue hypoxia occurs, which activates signaling pathways stimulating cell proliferation, angiogenesis, and death
Dulbecco’s Modified Eagle Environment (DMEM), fetal calf serum (FCS) and resazurine sodium salt were purchased from Sigma Aldrich (Munich, Germany)
Diagnosis and chemoprevention are essential for reducing the incidence of cancers
Summary
During tumor development tissue hypoxia occurs, which activates signaling pathways stimulating cell proliferation, angiogenesis, and death. Lymphocytes are an important part of the immune response to tumors because they inhibit tumorigenesis and kill cancer cells. There are tumor-derived factors that induce myelopoiesis, accumulation, and differentiation of tumorassociated macrophages (TAMs). These TAMs produce ROS and RNS in the tumor microenvironment, triggering a tumorinduced inflammation, and creating a vicious cycle between inflammation and cancer (Ardi et al, 2007; Reuter et al, 2010; Andrisic et al, 2018; de Souza et al, 2018). Platelets can promote angiogenesis through vascular endothelial growth factor (VEGF) secretion and protect tumor cells from the immune response. Cancer cells’ adaption to hypoxia is part of the malignant phenotype and aggressive tumor progression mechanism (Bambace and Holmes, 2011; Petrillo et al, 2018)
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