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 cane
extracts, a typical cultivar of southern Italy. We also explored the anticancer activity of the polyphenolrich
fraction of the extract on head and neck squamous carcinoma cells (HNSCC) and investigated the
underlying mechanism. Aqueous extracts were prepared at different pHs and extraction times and
the total phenolic and reducing sugar contents were estimated. Radical Scavenging Activity (RSA),
Ferric Reducing Antioxidant Power (FRAP), and Total Antioxidant Capacity (TAC) of the extracts
were measured. A polyphenol-rich fraction, accounting for 6.7% by weight and characterized mainly
by procyanidins and stilbenoids, was prepared from the extract obtained at pH 7 for 60 min. We
demonstrated that the extract exerted a cytotoxic effect on HNSCC cell lines by inducing cell cycle
arrest via cyclin downregulation and p21 upregulation, and by triggering apoptosis through caspase
cascade activation, PARP-1 cleavage, and an increase in the Bax/Bcl-2 ratio. We furnished evidence
that the polyphenol-rich fraction played the major role in the anticancer activity of the extract. These
outcomes highlighted grape canes from the "Greco" cultivar as a valuable source of polyphenols
that may represent good candidates for the design of innovative adjuvant therapies in the treatment
of HNSCC.