Antiproliferative activity of colchicine analogues on MDR-positive and MDR-negative human cancer cell lines

摘要: In this study the in vitro antitumor activity of a series 20 colchicine analogues was tested and compared with thiocolchicine on three different human cancer cell lines, two which express multidrug-resistance (MDR) phenotype. At concentrations from 1 nM to 100 microM, all compounds inhibited proliferation. The IC50 values indicate that fluorinated were most active compounds, similar decreasing order potency (IDN 5005 > IDN 5079 5080) MDR-expressing whereas effective compound MDR-negative MDA-MB 231 cells. A strong correlation (r = 0.94; P 0.004) found between obtained using MDR-positive lines. Conversely, cells did not show significant thereby suggesting some difference antiproliferative mechanism(s) analogues. Cell cycle analysis breast showed relationship blocking growth inhibition. agents MCF7 ADRr line, after 24 h culture, terms Interestingly, 72 h, when block subsided, consistent amount DNA fragmentation evident. extent block, measured as G2/G1 ratio, significantly correlated apoptosis rate expressed percentage both large number blocked underwent apoptotic pathway.