OBJECTIVE: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.
METHODS: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.
RESULTS: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.
CONCLUSION: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.
MAIN METHODS: A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay. Meanwhile, cell cycle regulation and apoptosis on MCF-7 cell were evaluated using flow cytometry. Regulation of cell cycle and apoptosis related genes expression was investigated by quantitative real time polymerase chain reaction (qRT-PCR), western blot and caspases activity analyses. Activation of oxidative stress on MCF-7 were evaluated by measuring ROS and GSH levels.
KEY FINDINGS: DK1 was found to possess selective cytotoxicity on breast cancer MCF-7 cell than normal MCF-10A cell. Flow cytometry cell cycle and AnnexinV/PI analyses reported that DK1 effectively arrested MCF-7 at G2/M phase and induced apoptosis after 72 h of incubation than curcumin. Upregulation of p53, p21 and downregulation of PLK-1 subsequently promote phosphorylation of CDC2 which were found contributed to the arrest of G2/M phase. Moreover, increased of reactive oxygen species and reduced of antioxidant glutathione level correlate with apoptosis observed with raised of cytochrome c and active caspase 9.
SIGNIFICANCE: DK1 was found to be more effective in inducing cell cycle arrest and apoptosis against MCF-7 cell with much higher selectivity index of MCF-10A/MCF-7 than curcumin, which might be contributed by the overexpression of p53 protein.
METHODS: 4T1 cancer cells were treated with kefir water in vitro to assess its antimigration and anti-invasion effects. BALB/c mice were injected with 4T1 cancer cells and treated orally with kefir water for 28 days.
RESULTS: Kefir water was cytotoxic toward 4T1 cells at IC50 (half-maximal inhibitory concentration) of 12.5 and 8.33 mg/mL for 48 and 72 hours, respectively. A significant reduction in tumor size and weight (0.9132 ± 0.219 g) and a substantial increase in helper T cells (5-fold) and cytotoxic T cells (7-fold) were observed in the kefir water-treated group. Proinflammatory and proangiogenic markers were significantly reduced in the kefir water-treated group.
CONCLUSIONS: Kefir water inhibited tumor proliferation in vitro and in vivo mainly through cancer cell apoptosis, immunomodulation by stimulating T helper cells and cytotoxic T cells, and anti-inflammatory, antimetastatic, and antiangiogenesis effects. This study brought out the potential of the probiotic beverage kefir water in cancer treatment.