Anti-Proliferative and Pro-Apoptotic Effects of Digested Aglianico Grape Pomace Extract in Human Colorectal Cancer Cells

Abstract

Grape pomace (GP)—the major by-product of winemaking processes—still contains bioactive molecules with known beneficial properties for human health, such as an antiradical scavenging activity or an antiproliferative activity of tumors. In vitro studies have demonstrated that GP polyphenols specifically influence colon cancer cell proliferation. In addition to previously published work, we tested the phenolic compounds of Aglianico GP following an in vitro simulated gastrointestinal digestion on colorectal cancer cell lines at different degrees of differentiation. Our experiments, using HT29 and SW480 cells, confirmed the anti-proliferative effect of GP gastrointestinal digested extract and provided intriguing insights on the way it influences the cancer cell features (i.e., viability, proliferation, and apoptosis). We observed that Aglianico GP extract showed a great ability to affect cell proliferation and apoptosis. Interestingly, both HT29 and SW480 cells produced a significant increase in Bax, and a significant increase in the Bax/Bcl-2 ratio and caspase-3. The gastrointestinal digested GP extract was previously characterized both for antioxidant activity and phenolic composition. As a result, the TPC and the antioxidant activity reached high values in the Aglianico GP digested extract, and the main compounds assessed by UHPLC-DAD were anthocyanins, phenolic acids, and flavonoids. This work shed light on the use of digested GP extract as a dietary ingredient, a very sustainable source of nutritional compounds with potential health benefits for colon cancer cell proliferation.

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“…Once biotransformed in less complex compounds such as phenolic acids, the generated metabolites and bioactive molecules will modulate the gut microbiota [45,47,48], exerting an effect similar to prebiotics by favoring the growth of beneficial bacteria and inhibiting the growth of pathogenic ones [47,49]. Studies have shown that the antioxidant and antiinflammatory activities exerted by the polyphenols act against metabolic disorders such as cancer, obesity, and diabetes via modulation of the gut microbiota [24,48,[50][51][52]. There is evidence that metabolic alterations induced by a high-fat diet can also be attenuated by polyphenols intake via activation of PPARα and GLUT4 [53].…”

Antioxidant and antiproliferative potentials of phenolic-rich extracts from biotransformed grape pomace in colorectal Cancer

“…Numerous studies have demonstrated the key role of cancer therapy in identifying compounds that induce cell apoptosis and play a key role in eliminating mutated hyperproliferating cells from the system. Phenolic compounds, with their antiproliferative and antitumor activities, are involved in the proliferation, differentiation, and apoptosis of various cancer cells, including colon cancer [ 4 , 39 ]. Also very important in terms of chemoprevention by phenolic compounds is their differential effect on cancer cells but not on normal cells [ 40 ].…”

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“…A substantial upregulation of Bax, as well as the Bax/Bcl-2 ratio and caspase-3, was observed in both HT29 and SW480 cells. UHPLC-DAD analysis revealed that anthocyanins, phenolic acids, and flavonoids were the primary components responsible for the elevated (total phenolic content) TPC and antioxidant activity in the Aglianico GP digested extract [ 91 ]. In 2021, Zhang and his co-workers studied the combined effect of chrysin and apigenin by suppressing the activity of P38-MAPK/AKT pathway in colorectal cancer.…”