The Antitumor Potential of Sicilian Grape Pomace Extract: A Balance between ROS-Mediated Autophagy and Apoptosis

• Published in: Biomolecules (Basel, Switzerland) Vol. 14; no. 9; p. 1111
• Main Authors: Affranchi, Federica, Di Liberto, Diana, Lauricella, Marianna, D'Anneo, Antonella, Calvaruso, Giuseppe, Pratelli, Giovanni, Carlisi, Daniela, De Blasio, Anna, Tesoriere, Luisa, Giuliano, Michela, Notaro, Antonietta, Emanuele, Sonia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.09.2024; MDPI
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Antioxidants; Antitumor activity; Antitumor agents; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; autophagy/apoptosis balance; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; By products; Calibration; Cancer therapies; Caspase-3; Cell activation; Cell cycle; Cell death; Cell Line, Tumor; Cell Survival - drug effects; Colon; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; DNA fragmentation; Ethylenediaminetetraacetic acid; Flavonoids; Functional foods & nutraceuticals; grape pomace; Humans; Medical research; Phagosomes; Phenolic acids; Plant Extracts - chemistry; Plant Extracts - pharmacology; Poly(ADP-ribose) polymerase; Polyphenols; Reactive oxygen species; Reactive Oxygen Species - metabolism; redox status; Seeds; Tumor cell lines; Tumor cells; Vitis - chemistry; Honduras; Italy; autophagy/apoptosis balance; polyphenols; grape pomace; redox status; antioxidants
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14091111

From the perspective of circular economy, it is extremely useful to recycle waste products for human health applications. Among the health-beneficial properties of bioactive phyto-compounds, grape pomace represents a precious source of bioactive molecules with potential antitumor properties. Here, we describe the effects of a Sicilian grape pomace hydroalcoholic extract (HE) in colon and breast cancer cells. The characterization of HE composition revealed the predominance of anthoxanthins and phenolic acids. HE treatment was more effective in reducing the viability of colon cancer cells, while breast cancer cells appeared more resistant. Indeed, while colon cancer cells underwent apoptosis, as shown by DNA fragmentation, caspase-3 activation, and PARP1 degradation, breast cancer cells seemed to not undergo apoptosis. To elucidate the underlying mechanisms, reactive oxygen species (ROS) were evaluated. Interestingly, ROS increased in both cell lines but, while in colon cancer, cells' ROS rapidly increased and progressively diminished over time, in breast cancer, cells' ROS increase was persistent up to 24 h. This effect was correlated with the induction of pro-survival autophagy, demonstrated by autophagosomes formation, autophagic markers increase, and protection by the antioxidant NAC. The autophagy inhibitor bafilomycin A1 significantly increased the HE effects in breast cancer cells but not in colon cancer cells. Overall, our data provide evidence that HE efficacy in tumor cells depends on a balance between ROS-mediated autophagy and apoptosis. Therefore, inhibiting pro-survival autophagy may be a tool to target those cells that appear more resistant to the effect of HE.