CLC-107, a novel furopyrazole compound, was examined for cells proliferation inhibition effect on human or mouse cancer cell lines include leukemia cells (HL-60, U-937, RAW 264.7 and WEHI-3), lung cancer carcinoma (CH27, A-549 and H1355), hepatoblastoma (Hep G2 and Hep 3B) and colon adenocarcinoma (COLO 205). We used propidium iodide (PI) incorporation and MTT assay to determine the proliferation rate on CLC-107 treatment. Our data showed after 48 h of treatment with CLC-107, concentration- and time-dependent decrease in cell proliferation rate of U-937 and WEHI-3 cells. CLC-107 treated U-937 and WEHI-3 cells presented typical characteristics of apoptosis as further evidenced by TUNEL/DAPI double-staining and internucleosomal DNA fragmentation by electrophoresis. CLC-107 obviously induced loss of mitochondrial membrane potential in U-937 cells treated for 24 h, and apparent release of cytosolic cytochrome c, down-regulation of Bcl-2 and up-regulation of Bax protein by Western blot analysis. CLC-107 induced apoptosis was mainly mediated by activation of caspase-3 by caspases activity assay. These results indicated that the ability of CLC-107 to inhibit cell proliferation might be inducted apoptosis on U-937 leukemia cells.?
