Cytotoxic Activity of Sicilian Red- and White-Grape Seed Oils on Human Liver and Colorectal Cancer Cells

Seed oils from Sicilian white (WGSO) and red grapes (RGSO) were examined for their possible cytotoxic effect on HepG2 liver and CaCo-2 colorectal cancer cells, the latter also induced to intestinal differentiation. Half maximal inhibitory dilution (ID50) values were obtained from viability assays, excluding RGSO-treated HepG2 and differentiated CaCo-2 cells exposed to both oils, which were unresponsive. Cell morphology and cycle status, reactive oxygen species (ROS) production, and the levels of cytoprotection, regulated cell death (RCD), and autophagy markers were evaluated. No occurrence of canonical apoptosis was proven in any experimental condition. In HepG2 cells, WGSO ID50 primarily triggered autophagy collapse, as evidenced by modulation of Beclin-1, p62 and LC3 markers, initiating a cascade of metabolic disturbances that led to oxidative stress reaction and mild inflammatory signaling. In CaCo-2 cells, WGSO ID50 mainly elicited a strong ROS-mediated cell injury without major alterations in autophagy, with transient activation but incomplete execution of pyroptotic and necroptotic effectors (gasdermin-D, pMLKL and HMGB1). In the same cells, RGSO ID50 induced a weaker metabolic perturbation with transient activation of multiple RCD pathways and concomitant autophagy inhibition. Research findings revealed distinct damage-inducing properties linked to oils’ chemical profiles, underscoring their prospective utilization as beneficial bioactive supplements.