Identification of bioactive compounds in Lactobacillus paracasei subsp. paracasei NTU 101-fermented reconstituted skimmed milk and their anti-cancer effect in combination with 5-fluorouracil on colorectal cancer cells

Abstract

Chemotherapy is currently used to treat colorectal cancer (CRC), the most common cancer worldwide. However, chemotherapeutic drugs are limited by severe side effects or drug resistance. In this study, bioactive compound(s), a mixture of palmitic acid, stearic acid, and glyceryl 1,3-dipalmitate (PSG), in Lactobacillus paracasei subsp. paracasei NTU 101-fermented reconstituted skimmed milk ethanol extract (NTU 101-FMEE) were isolated and identified. PSG (1 : 1.5 : 6.3) at 125 μg mL⁻¹ could significantly decrease CRC cell viability at dosages that were not cytotoxic to healthy colon epithelial cells or macrophages. Moreover, the inhibitory effect of the combination of 62.5 μg mL⁻¹ PSG (1 : 1.5 : 6.3) and 5-fluorouracil (5-FU) was significantly higher than that of 5-FU alone (p < 0.05). PSG up-regulated the activities of apoptosis-related proteins and down-regulated the nuclear factor-κB signaling pathway compared to the levels in the control group. Overall, PSG purified from NTU 101-FMEE possesses the potential to ameliorate CRC by improving the effects of adjuvant chemotherapy drugs and reducing side effects.