Effects of Protease-Hydrolyzed and Cordyceps militaris-Fermented Sea Cucumber Viscera Hydrolysates on Cellular Function and Energy Metabolism in HCT116 Cells.

Colorectal cancer (CRC) remains a major global health concern. Marine by-products are increasingly recognized as promising sources of functional ingredients with diverse bio-activities. This study investigated the effects of sea cucumber viscera hydrolysates prepared by protease hydrolysis (SVH) and further fermented with Cordyceps militaris (FSVH) on cellular function and energy metabolism in HCT116 cells. Cell viability, apoptosis, migration, and invasion were evaluated using CCK-8, flow cytometry, wound healing, and Transwell assays. Cellular energy metabolism was assessed by measuring glucose uptake, lactate production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR). The results showed that SVH and FSVH exhibited distinct biological activity profiles in HCT116 cells. Both SVH and FSVH induced apoptosis and inhibited the migration and invasion of HCT116 cells. Both treatments affected glucose metabolism and mitochondrial respiratory function, including glucose uptake, lactate production, mitochondrial respiration, and glycolytic activity. SVH exhibited stronger inhibitory effects on glycolysis-related parameters, whereas FSVH showed greater effects on mitochondrial respiratory capacity. These findings indicate that C. militaris fermentation modified rather than simply enhanced the biological properties of sea cucumber viscera hydrolysates, resulting in distinct effects on cellular function and energy metabolism. This study highlights the potential application of sea cucumber viscera hydrolysates for the value-added utilization of marine processing by-products.