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Dysregulation of microRNAs (miRNAs) in colorectal cancer provides important opportunities for the development of future miRNA‑based therapies. The present study aimed to assess the role of miRNA‑630 (miR‑630) expression in colorectal cancer. HCT116 human colorectal cancer cells were transfected with miR‑630 inhibitor, mimic or control miRNA, and the effects of miR‑630 dysregulation on cell viability, proliferation and apoptosis were analyzed using MTT and bromodeoxyuridine assays, and an annexin V‑fluorescein isothiocyanate cell apoptosis kit, respectively. In addition, the changes in the protein expression of proliferation‑associated and AKT signaling pathway proteins were analyzed by western blot analysis. The results of the present study demonstrated that overexpression of miR‑630 significantly promoted HCT116 cell proliferation however inhibited apoptosis. Furthermore, miR‑630 overexpression reduced the protein expression of p27, BCL2‑associated X apoptosis regulator, procaspase‑3 and active caspase‑3, and increased the levels of phosphorylated‑AKT and BCL2 apoptosis regulator. The suppression of miR‑630 led to the opposite results. In conclusion, the present findings suggested that miR‑630 may function as an oncogenic miRNA in colorectal cancer, and may promote cellular proliferation and inhibit apoptosis, through the regulation of the expression of p27 and the AKT signaling pathway. The present study suggested that the inhibition of miR‑630 may have potential as an alternative therapeutic strategy for the treatment of patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Norcantharidin (NCTD) is a Chinese FDA approved, chemically synthesized drug for cancer treatment. The effect of NCTD on signaling proteins of EGFR and c-Met was systematically elucidated in current study.Methods: Two human colon cancer cell lines, HCT116 and HT29, were used as model systems to investigate the anti-cancer molecular mechanism of NCTD. Cell cycle arrest and early/late apoptosis were analyzed by flow cytometry. The levels of EGFR, phospho-EGFR, c-Met, phospho-c-Met and other related proteins were quantified by western blot analysis.Results: NCTD induced cell cycle arrest at G2/M phase in both cell lines. The early and late apoptosis was also observed. Further investigation indicated that NCTD suppressed not only the expression of the total EGFR and the phosphorylated EGFR but also the expression of the total c-Met and the phosphorylated c-Met in colon cancer cells. Moreover, EGFR expression could be mostly restored by co-treatment with MG132, a proteasome inhibitor. In addition, NCTD-induced cell death was comparable to that of the anti-cancer drug gefitinib, a tyrosine kinase inhibitor for EGFR, based on the immunoblot analysis of the expressed proteins after the drug treatment.Conclusions: NCTD might be a useful and inexpensive drug candidate to substitute for gefitinib to serve the treatment needs of cancer patients. [ABSTRACT FROM AUTHOR]

Most β-d-xylosides with hydrophobic aglycones are nontoxic primers for glycosaminoglycan assembly in animal cells. However, when Ebselen was conjugated to d-xylose, d-glucose, d-galactose, and d-lactose (8A-D), only Ebselen β-d-xyloside (8A) showed significant cytotoxicity in human cancer cells. The following facts indicated that the aglycone Ebselen and β-d-xyloside primed glycosaminoglycans co-contributed to the observed cytotoxicity: 1. Ebselen induced S phase cell cycle arrest, whereas 8A induced G2/M cell cycle arrest; 2. 8A augmented early and late phase cancer cell apoptosis significantly compared to that of Ebselen and 8B-D; 3. Both 8A and phenyl-β-d-xyloside primed glycosaminoglycans with similar disaccharide compositions in CHO-pgsA745 cells; 4. Glycosaminoglycans could be detected inside of cells only when treated with 8A, indicating Ebselen contributed to the unique property of intracellular localization of the primed glycosaminoglycans. Thus, 8A represents a lead compound for the development of novel antitumor strategy by targeting glycosaminoglycans. [ABSTRACT FROM AUTHOR]