Investigation of lactic acid bacteria (LAB) induced postbiotic effect on the sensitivity of colorectal cancer cells to 5-Florouracil (5-FU)

The most important chemotherapeutic molecule used in colorectal cancers is 5-Fluorouracil. Insensitivity developed against 5-FU in some patients adversely affects the prognosis. Most deaths are attributed to the metastasis of cells insensitive to chemotherapy. The hypothesis that adjuvant interventions based on probiotic and postbiotic use in conjunction with chemotherapy will positively impact clinical prognosis is a potential strategy in treatment. The beneficial effects observed with live probiotic microorganisms are sometimes short-lived, ineffective, and uncertain. These disadvantages increase the importance of postbiotics, which are metabolic products derived from probiotics. Cancer cells can survive under severe stress conditions by utilizing autophagy. This process promotes tumour growth and increases resistance to treatment. It has been observed that cancer cells isolated from tumours where autophagy is inhibited are more sensitive to exogenous stress stimuli compared to cancer cells where autophagy inhibition has not been performed. There is no study in the literature reporting whether the autophagy effect is present in the chemotherapeutic response created by the combined application of lactic acid bacteria-derived postbiotics and chemotherapy. For this purpose, in our study, autophagic processes were examined by treating 5-FU-sensitive colorectal adenocarcinoma (HT-29), colorectal adenocarcinoma (Caco-2) with proven 5-FU resistance in the literature, and a control group of normal human fibroblast (BJ) cells with 5-FU and/or postbiotics (derived from LAB) in a cell culture environment. The postbiotics used were obtained from probiotics isolated from yogurt samples prepared using traditional methods in the Ankara region. The postbiotic with the highest antioxidant capacity was used in our study. The effective value of 5-FU has been determined in the culture medium. Subsequently, the effect of 5-FU and/or postbiotic combination application on autophagic pathways was determined by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western Blot. In conclusion, this study reports that LAB derived postbiotics can inhibit autophagy signaling pathway induced by 5-FU treatment in colorectal cancer cells. This finding holds pioneering significance for future studies. Our research will shed light on pharmacovigilance studies that will provide a more accurate projection for determining the effectiveness of drugs and establishing treatment dosages in cell culture.