Recent research of 1,2,3-triazole's pharmacological effects became much more appealing and promising for anticancer agents design. 1,2,3-Triazoles conjugated with a wide range of moieties were reported to exhibit potent anticancer activity. DYC-279 is one of newly synthesized compound by our group which is one of a series of 1,2,3-triazoleedithiocarbamate hybrids with general structure by our research group(as shown Figure1 A). In the present study, we revealed that DYC-279 can inhibit the proliferation of HepG-2 cells in a dose- and time-dependent manner using the MTT test. No cross-resistance was detected. FACS-based cell cycle analysis revealed a significant increase in the G2/M phase and depletion in the G0/G1 phase populations. A concomitant down-regulation of cyclin D1 and up-regulation of CDC2 and Cyclin B1 in hepatocellular carcinoma HepG-2 cell was detected by Western blot. It means that DYC-279 could increase the expression of CyclinB1 and the phosphorylation of Cdc2 in concentration -dependent manners with decreasing the dephosphorylation of Cdc2 and in hepatocellular carcinoma HepG-2 cell in vitro. Cyclin D1 is the key protein in G1 phase and it has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of these genes, which alters cell cycle progression, is observed frequently in a variety of tumors and may contribute to tumorigenesis. Western blot analysis revealed that DYC-279 induced the activation of caspase-9 and the release of cytochrome C (Cyto C) from the mitochondria to the cytosol. Furthermore, the pro-apoptotic factor, Bax, was upregulated and the anti-apoptotic factor, Bcl-2, was downregulated, eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. The results demonstrated that DYC-279 inhibits proliferation and induces apoptosis of HepG-2 cells human cells in vitro. The induction of apoptosis appears to occur through the upregulation of Bax, the downregulation of Bcl-2, the release of Cyto C from the mitochondria to the cytosol and the activation of caspase-9, which subsequently trigger major apoptotic cascades. DYC-279 has potent antitumor activity in HepG-2 cells human cells and may be used as a novel effective reagent in the treatment of colon cancer.

Primary study of vitro antitumor effect of DYC-279 on human hepatocellular carcinoma HepG-2 cells

247th National Meeting (2014)

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