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  • Title: Effects of YC-1 on hypoxia-inducible factor 1-driven transcription activity, cell proliferative vitality, and apoptosis in hypoxic human pancreatic cancer cells.
    Author: Zhao Q, Du J, Gu H, Teng X, Zhang Q, Qin H, Liu N.
    Journal: Pancreas; 2007 Mar; 34(2):242-7. PubMed ID: 17312464.
    Abstract:
    OBJECTIVES: To investigate the effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) on HIF-1-driven transcription activity, cell proliferative vitality, and apoptosis in hypoxic human pancreatic cancer cells. METHODS: Human pancreatic cancer PC-3 cells were incubated under normoxic or hypoxic conditions. YC-1 was added to the media with different concentrations. The HIF-1alpha protein expression was detected by means of immunocytochemical staining and Western blotting. Semiquantitative reverse transcriptase polymerase chain reaction was used to determine the mRNA expression of HIF-1alpha, vascular endothelial growth factor (VEGF), and glucose phosphate isomerase (GPI). A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry were used to detect the cells' proliferative vitality and apoptosis. RESULTS: Hypoxic PC-3 cells expressed a higher level of HIF-alpha protein in nucleus compared with the normoxic controls. When the dose of YC-1 was at 100 micromol/L, the expression location of HIF-alpha shifted from nucleus to cytoplasm. Western blotting revealed that YC-1 reduced the level of HIF-1alpha protein expression, and the inhibitory effect was dose dependent. Moreover, YC-1 dose dependently inhibited mRNA expression levels of VEGF and GPI in hypoxic cells. YC-1 inhibited proliferative vitality and induced apoptosis of hypoxic PC-3 cells in a dose-dependent manner. CONCLUSIONS: YC-1 inhibits HIF-1alpha expression in hypoxic pancreatic cancer cells, which is accompanied by the translocation of HIF-1alpha from nucleus to cytoplasm, decreased mRNA expression of VEGF and GPI, reduced cell proliferative vitality, and increased apoptosis. These results suggest that HIF-1 is a potential therapeutic target for pancreatic cancer.
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