Synthesis and anticancer activity of some pyrimidine derivatives with aryl urea moieties as apoptosis-inducing agents.

A new series of pyrimidine derivatives containing aryl urea moieties was designed and synthesized. The anticancer activities of all compounds were evaluated in vitro against colon and prostat cancer cell lines by MTT assay. Among these compounds, 4b exhibited the highest cytotoxic activity against SW480 cancer cell line with IC50 value of 11.08 µM. Mechanistic studies showed that compound 4b arrested cell cycle at G2/M phase and induced apoptosis through upregulating Bax, Ikb-α and cleaved PARP and downregulating Bcl-2 expression levels. Moreover, compound 4b induced loss of mitochondrial membrane potential in SW480 cells. These results suggest that pyrimidine with urea moieties could be a template for designing new anticancer agents.

The Cellular Uptake and Apoptotic Efficiency of Colchicine is Correlated with Downregulation of MMP-9 mRNA Expression in SW480 Colon Cancer Cells.

BACKGROUND: Colchicine, a tricyclic alkaloid, is commonly used in treatment due to its antiinflammatory and anti-fibrotic effects. Besides its toxicity at high doses, colchicine is reported for its potential anticancer effects at lower concentrations. The present study aimed to evaluate the anticancer effects of colchicine in SW480 cells. METHODS: The effect of colchicine on cell proliferation was determined by MTT assay. The cellular colchicine uptake was measured by HPLC analysis. The apoptotic effects was evaluated by annexin v binding assay and MMP-9 mRNA expression was determined by RT-PCR experiments. RESULTS: Colchicine showed significant cytotoxicity at 10 ng/ml and higher concentrations and caused a cell cycle arrest of SW480 cells at G2/M phase. The results of HPLC analysis showed that colchicine uptake was increased in correlation with treated concentrations. Colchicine concentrations have increased the amount of apoptotic cell population. The elisa and western blot measurements showed that colchicine led to nuclear translocation of NF-κB proteins and increased caspase levels. The real time PCR experiments showed that colchicine has inhibitory effect on MMP-9 mRNA expression in a concentration dependent manner. CONCLUSION: These results illustrated that low dose colchicine efficiently induced cell death and apoptosis of SW480 cells and the inhibition of MMP-9 mRNA levels was significantly correlated with the amount of cellular colchicine uptake, suggesting that colchicine has a potential value in the treatment of human colorectal cancer.