Title:The Cellular Uptake and Apoptotic Efficiency of Colchicine is Correlated with Downregulation of MMP-9 mRNA Expression in SW480 Colon Cancer Cells
VOLUME: 18 ISSUE: 13
Author(s):Nuri Ozmen, Ecem Kaya-Sezginer and Filiz Bakar-Ates*
Affiliation:Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara
Keywords:Colchicine, cellular uptake, cytotoxicity, SW480, apoptosis, cell cycle, MMP-9.
Abstract: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.
