Secretion metabolites of dairy Kluyveromyces marxianus AS41 isolated as probiotic, induces apoptosis in different human cancer cell lines and exhibit anti-pathogenic effects

Abstract

This study aimed to the isolation, molecular identification, and probiotic characterization of yeasts from traditional Iranian dairy products as well the investigation of proapoptotic effects of yeasts secretion metabolites on different human epithelial cancer and normal cell lines. The expression levels of key genes in intrinsic/extrinsic apoptosis pathways were also studied. Based on prescreening tests, among all yeasts, K. marxianus AS41 showed the highest anticancer activity in AGS cells (53.8% mortality), high tolerance to low pH (71% survival rate) and high bile salt (83% survival rate) conditions, high anti-pathogenic activities, and susceptibility to conventional antifungal. Moreover, K. marxianus AS41 secretion metabolites, significantly downregulated Bcl-2 and upregulated BAD and CASP 9 gene expression in the AGS cancer cells compared to 5-Fluorouracil as positive control. Besides, in all epithelial cancer cells the expression level of Fas-R, CSAP 8 and CASP 3 upregulated significantly, suggested that extrinsic apoptosis pathway is the main path for apoptosis of malignant cells. Finally, K. marxianus AS41 isolated from dairy products can be introduced as probiotics and its secretion metabolites affect metabolic activity and exhibit proapoptotic activity on epithelial cancer cells with non-significant effect on normal cells suggesting that further studies are required to explain the exact mechanism of apoptosis induction by K. marxianus AS41 culture supernatant extracts.