Microbial valorization of pomegranate peel pectin into pectic oligosaccharides with selective anticancer activities: in vitro and in silico evaluation.

Pomegranate peel, a major by-product of processing, is rich in water-soluble pectin made of D-galacturonic acid units with α (1-4) linkage. Efficiently converting pomegranate peel into safe bioactive principles minimizes waste in the fruit industry and opens new avenues in functional foods. In this work, pomegranate pectin was enzymatically depolymerized with extracellular pectinases from Streptomyces hydrogenans YAM1 to generate pectic oligosaccharides (POS). Products were characterized by TLC and LC-ESI-MS, which indicated unsaturated mono-, di-, and trigalacturonic acids among the main species. Antioxidant activity was maximal at 5 mg mL⁻¹, as detected by the DPPH assay. The anticancer effects of the obtained POS were evaluated by assessing the viability of breast cancer (MCF-7), colorectal adenocarcinoma (Caco2), and neuroblastoma (SH-SY5Y) cells using MTT and flow cytometry assays. Cytotoxicity was also evaluated on normal cells (L929 and HUVEC). The results revealed that at 30 mg mL⁻¹, POS reduced the viability of MCF-7, Caco-2, and SH-SY5Y cancerous cells to < 20% while exhibiting no significant toxicity toward L929 and HUVEC normal cells. The observed efficacy against various cancer cells, without inducing cytotoxicity in healthy cells, distinguishes this compound from other anticancer agents. In the theoretical evaluation using the MM/PBSA method, the most suitable compounds were tetra-galacturonic acid and Δ4,5-unsaturated tri-galacturonate, whose binding free energies to the active site of the Gal-3 receptor were - 128.38 ± 21.51 kJ/mol and - 124.16 ± 23.16 kJ/mol, respectively. These findings support its potential as a unique nutritional compound for preventing and controlling cancer cell growth, advancing the development of next-generation functional pharmaceutical supplements.