Phytochemical Content of Muscadine Grape Promoting Apoptosis and Inhibiting Cancer Cell Growth to Prevent Cancer Progression

Muscadine grape ( Vitis rotundifolia ) is a rich source of bioactive phytochemicals; however, links between genotype-dependent phytochemical diversity and anticancer activity remain poorly defined. Here, fifty muscadine grape genotypes were systematically evaluated for phenolic composition, antioxidant capacity, and anticancer efficacy. Total phenolic content, total flavonoid content, and DPPH radical scavenging activity varied markedly among genotypes, indicating substantial biochemical diversity. Targeted HPLC analysis revealed pronounced genotypic differences in major stilbenes (resveratrol, viniferin, and pterostilbene) and catechin derivatives, with resveratrol and epicatechin contributing most strongly to antioxidant capacity. Biological relevance was confirmed using in vitro cancer models. Muscadine grape extracts significantly reduced cell viability in A549 (lung), LNCaP (prostate), and Caco-2 (colon) cancer cell lines in a genotype-dependent manner following 48 h exposure, with IC₅₀ values ranging from 300 to 450 µg mL⁻¹. Notably, genotypes such as Southern Home exhibited elevated phytochemical accumulation and pronounced antiproliferative activity. Pearson’s correlation and multivariate analyses, including hierarchical clustering, principal component analysis, and the multi-trait genotype–ideotype distance index (MGIDI), identified elite genotypes with favorable integrated biochemical and biological profiles. Collectively, these findings demonstrate that phytochemical-rich muscadine grape genotypes exert pronounced antiproliferative effects and support their potential application in functional foods and nutraceutical strategies for cancer prevention.