Extracts ofElaeagnus multifloraThunb. fruit fermented by lactic acid bacteria inhibit SW480 human colon adenocarcinoma via induction of cell cycle arrest and suppression of metastatic potential

Elaeagnus multifloraThunb. (cherry silverberry, CS) is an underutilized fruit with notable phytochemical profile and biological activities. However, there are few studies on cancer inhibitory effect using fermented CS fruits. This study aimed to develop fermented CS fruits using lactic acid bacteria and investigate its anticolorectal cancer (CRC) property and phenolic composition. SW480 CRC cells were treated with aqueous extracts of CS fermented by single and coculture ofLactobacillus plantarumandL. casei. The extracts of fermented CS exhibited greater antiproliferative activity and anticlonogenicity in comparison with the unfermented extract and the control. Among the extracts of CS fruits, the ones fermented by the coculture (LPLC) showed the most potent tumor suppression property, at 25 to 50 mu g/mL, by induction of cell cycle arrest at the S and G2/M phases, downregulating cyclins and its dependent kinases while increasing tumor suppressor proteins p27 and p53. LPLC also exerted its tumor suppression effect by inhibiting the chemotactic motility and invasiveness of SW480 cells, downregulating matrix metalloproteinase-9, and PI3K/AKT/mTOR pathways and upregulating TIMP-9, and E-cadherin. HPLC-PDA analysis revealed that the levels of major flavonoids in CS extracts, namely, catechin, epigallocatechin, epicatechin, epigallocatechin gallate, rutin, naringin, and quercetin, were enhanced by fermentation withL. plantarumandL. caseiin coculture. Overall, this study showed that the extracts of fermented CS have augmented and multifaceted anticancer property and can be utilized in the development of functional food or ingredient for the prevention of CRC. Practical Application Elaeagnus multiflora, commonly known as cherry silverberry, has been proven to contain bioactive components and possesses high functionality. However, due to limited shelf-life as a fresh commodity, development of novel product is essential. Fermentation is a beneficial process employed in the food industry to enhance the shelf stability, nutritional, sensory, and functional properties of food products. The present study has explored the possibility of adding value to an underutilized fruit, cherry silverberry, through the process of fermentation, making it as a potential source of functional food and ingredient for the prevention of colorectal cancer.