Polyphenol Extract from "Greco" Grape Canes: Characterization, Antioxidant Capacity, and Antitumor Effects on Cal-33 and JHU-SCC-011 Head and Neck Squamous Cell Carcinoma

In the current study, we determined the antioxidant properties of "Greco" grape caneextracts, a typical cultivar of southern Italy. We also explored the anticancer activity of the polyphenolrichfraction of the extract on head and neck squamous carcinoma cells (HNSCC) and investigated theunderlying mechanism. Aqueous extracts were prepared at different pHs and extraction times andthe total phenolic and reducing sugar contents were estimated. Radical Scavenging Activity (RSA),Ferric Reducing Antioxidant Power (FRAP), and Total Antioxidant Capacity (TAC) of the extractswere measured. A polyphenol-rich fraction, accounting for 6.7% by weight and characterized mainlyby procyanidins and stilbenoids, was prepared from the extract obtained at pH 7 for 60 min. Wedemonstrated that the extract exerted a cytotoxic effect on HNSCC cell lines by inducing cell cyclearrest via cyclin downregulation and p21 upregulation, and by triggering apoptosis through caspasecascade activation, PARP-1 cleavage, and an increase in the Bax/Bcl-2 ratio. We furnished evidencethat the polyphenol-rich fraction played the major role in the anticancer activity of the extract. Theseoutcomes highlighted grape canes from the "Greco" cultivar as a valuable source of polyphenolsthat may represent good candidates for the design of innovative adjuvant therapies in the treatmentof HNSCC.