Abstract
Colon cancer is the most common type of malignant tumor. The cytotoxicity effect of lactic acid bacteria may be active by inhibiting cancer cell proliferation, producing anticancer compounds, and inducing apoptosis in cancer cells, but the mechanism is unclear. Our previous study revealed that Lactobacillus acidophilus KLDS1.0901 has good probiotic properties. In this study, We screened out the highest inhibition rate of L. acidophilus KLDS1.0901 and assessed the effects on the proliferation of HT-29, Caco-2, and IEC-6 cells. Then, the apoptosis mechanism of HT-29 cells was studied when treated with L. acidophilus KLDS1.0901. Results showed that L. acidophilus KLDS1.0901 inhibited the proliferation of HT-29 and Caco-2 cells in a dose-dependent manner and reached the maximum under the condition of multiplicity of infection (MOI) = 100 (rate of Lactobacillus to cells) at 48 h. With the increase in time and MOI, reactive oxygen species in HT-29 cells, the apoptosis rates of HT-29 cells were increased, and the amount of blue fluorescence of the cells was also increased after Hoechst 33258 staining. Furthermore, L. acidophilus KLDS1.0901 reduced the mitochondrial membrane potential of HT-29 cells. Notably, 1,133 differentially expressed genes were screened by transcriptomics research, including 531 up-regulated genes and 602 down-regulated genes. These genes were involved in the nuclear factor κB and PI3K-AKT signaling pathways related to the apoptosis of HT-29 cells. These findings suggested that L. acidophilus KLDS1.0901 has the potential to be used in the development of a new type of functional foods for adjuvant treatment of colon cancer.
Highlights
Colon cancer is the fourth leading cause of cancer death globally, with more than one million cases diagnosed each year worldwide, and it is a multifactorial disease involving genetic, environmental, and lifestyle risk factors (Ferlay et al, 2015)
HT-29 cells treated with L. acidophilus KLDS1.0901 showed a significant (p < 0.05) reduction of cell proliferation compared with nontreated cells
5-FU was a significant difference (p < 0.05) at 12, 24, and 48 h (Figure 1D). These results indicated that L. acidophilus KLDS1.0901 inhibited the growth of HT-29 and Caco-2 cells, and the viability rate of IEC-6 cells was not affected
Summary
Colon cancer is the fourth leading cause of cancer death globally, with more than one million cases diagnosed each year worldwide, and it is a multifactorial disease involving genetic, environmental, and lifestyle risk factors (Ferlay et al, 2015). 5-Fluorouracil (5-FU) and oxaliplatin are the most effective drugs for the treatment of colon cancer. These treatments are expensive and have some side effects. A randomized trial conducted on a total of 398 subjects containing both men and women has shown that there is a lower rate of appearance of moderate and higher atypia graded tumors when taking Lactobacillus casei. It suggested the prophylactic implication of probiotics in colorectal cancer (Ishikawa et al, 2005). A randomized clinical trial with larger sample size, proper randomization process, proper analysis, and verification must be conducted to create more comprehensive and specific evidence to support the theory
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