Dealcoholated red wine induces autophagic and apoptotic cell death in an osteosarcoma cell line

• Lyophilized red wine is a mixture of bioactive compounds acting in synergy to inhibit cell proliferation.
• Antioxidant capacity of lyophilized red wine is independent from its biological effects on cancer cells.
• Lyophilized red wine inhibits proliferation via types I/II cell death, e.g., autophagy and apoptosis.

Until recently, the supposed preventive effects of red wine against cardiovascular diseases, the so-called “French Paradox”, has been associated to its antioxidant properties. The interest in the anticancer capacity of polyphenols present in red wine strongly increased consequently to the enormous number of studies on resveratrol. In this study, using lyophilized red wine, we present evidence that its anticancer effect in a cellular model is mediated by apoptotic and autophagic cell death. Using a human osteosarcoma cell line, U2Os, we found that the lyophilized red wine was cytotoxic in a dose-dependent manner with a maximum effect in the range of 100–200 μg/ml equivalents of gallic acid. A mixed phenotype of types I/II cell death was evidenced by means of specific assays following treatment of U2Os with lyophilized red wine, e.g., autophagy and apoptosis. We found that cell death induced by lyophilized red wine proceeded through a mechanism independent from its anti-oxidant activity and involving the inhibition of PI3K/Akt kinase signaling. Considering the relative low concentration of each single bioactive compound in lyophilized red wine, our study suggests the activation of synergistic mechanism able to inhibit growth in malignant cells.

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