The endocytic protein dynamin II (dynII) is a 100-kDa GTPase enzyme best known for its participation in cell cycle progression and role in centrosome cohesion and cytokinesis. Myristyl trimethyl ammonium bromide (MitMAB) is a novel inhibitor of dynII GTPase activity with IC50 value of 8.4 ± 5.79 μM. It also inhibits dynI GTPase activity with IC50 value of 2.26 ± 0.53 μM. HeLa, H460, and SW480 cancer cells were treated with various concentrations of MitMAB for 7 d. Antiproliferative effect of MitMAB in these cells with a 50% reduction in colony formation was confiemed at concentration of ∼0.5 μM indicating MitMAB inhibited cell proliferation and reduce viability in a range of cancer cells. Asynchronously growing HeLa cells were treated for 48 h with MitMAB. Consistent with its effect on cell viability, it increased the sub-G1 (<2N DNA content) population, indicating apoptosis. G1 and S phase populations decreased, whereas the population of cells containing 4N DNA content (G2-M) increased. Therefore, MitMAB disrupted cell cycle progression and caused cytokinesis failure [1].
作用机制
MitMAB inhibits dynamin GTPase activity by disrupting the PH (pleckstrin homology) domain-phospholipid interaction .
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