RESUMO
BACKGROUND AND OBJECTIVE: Ensuring colon homeostasis is of significant influence on colon cancer and delicate balance is maintained by a healthy human gut microbiota. Probiotics can modulate the diversity of the gut microbiome and prevent colon cancer. Metabolites/byproducts generated by microbial metabolism significantly impact the healthy colonic environment. Hesperidin is a polyphenolic plant compound well known for its anticancer properties. However, low bioavailability of hesperidin after digestion impedes its effectiveness. CYP2W1 is a newly discovered oncofetal gene with an unknown function. CYP2W1 gene expression peaks during embryonic development and is suddenly silenced immediately after birth. Only in the case of some types of cancer, particularly colorectal and hepatocellular carcinomas, this gene is reactivated and its expression is correlated with the severity of the disease. This study aimed to investigate the effects of hesperidin-treated Lacticaseibacillus rhamnosus GG (LGG) cell-free supernatants on CaCo2 colon cancer cell viability and CYP2W1 gene expression. METHODS: Alamar Blue cell viability assay was used to investigate the cytotoxic effect of cell-free supernatant of LGG grown in the presence of hesperidin on CaCo2 cells. To observe the effect of cell-free supernatants of LGG on the expression of CYP2W1 gene, qRT-PCR was performed. RESULTS: Five times diluted hesperidin treated cell-free supernatant (CFS) concentration considerably reduced CaCo2 colon cancer cell viability. Furthermore, CYP2W1 gene expression was similarly reduced following CFS treatments and nearly silenced under probiotic bacteria CFS treatment. CONCLUSION: The CYP2W1 gene expression was strongly reduced by cell-free supernatants derived from LGG culture, with or without hesperidin. This suggests that the suppression may be due to bacterial byproducts rather than hesperidin. Therefore, the CYP2W1 gene in the case of deregulation of these metabolites may cause CYP2W1-related colon cancer cell proliferation.
Assuntos
Neoplasias do Colo , Hesperidina , Lacticaseibacillus rhamnosus , Humanos , Hesperidina/farmacologia , Células CACO-2 , Sobrevivência Celular , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Expressão Gênica , Família 2 do Citocromo P450RESUMO
BACKGROUND: Patients with multiple sclerosis (MS) have significantly lower vitamin D levels. Cholesterol is known to be the precursor for vitamin D synthesis, and cholesterol removal is regulated by cholesterol 7α-hydroxylase (CYP7A1) in the liver and cholesterol 24S-hydroxylase (CYP46A1) in the brain. In this study, single nucleotide polymorphisms (SNPs) within the genes CYP7A1 (rs3808607) and CYP46A1 (rs754203) were investigated for their effects on serum lipid profiles, vitamin D levels, and the risk of developing MS. METHODS: Patients with MS (n = 191) and controls (n = 100) were tested using the PCR-RFLP method to determine their genotypes for rs3808607 and rs754203 SNPs. RESULTS: The minor (C) allele frequency for CYP7A1 rs3808607 variation was 0.380 in patients with MS and 0.305 in control subjects (P = .074). For CYP46A1 rs754203, the frequencies of the minor (C) allele were 0.272 and 0.250 in patients and control subjects, respectively (P = .563). Serum vitamin D (25(OH)D3) concentrations were significantly lower in patients than in control subjects (P = .002). The CYP46A1 rs754203 SNP was associated with total cholesterol levels in patients, whereas the CYP7A1 rs3808607 variant was not associated with serum lipid parameters or vitamin D levels in patients or control subjects. CONCLUSION: CYP7A1 rs3808607 and CYP46A1 rs754203 variations are not likely to confer an independent risk for MS development in the Turkish population. To the best of our knowledge, this is the first study to investigate the association between CYP46A1 rs754203 and MS risk.