A. A. Philchenkov1, M. P. Zavelevich1, N. N. Khranovskaya2, L. A. Zaika3, A. I. Potopalsky3
The novel anticancer drug amitosine representing the mixture of thiophosphamide-modified alkaloids from Chelidonium majus L. has been reported to inhibit growth of various solid tumors in vivo. However, its antileukemic activity as well as the mechanisms of anticancer action have not been yet extensively examined. In this study, amitosine treatment at a dose of 100–250 ?g/mL for 24 h resulted in dose-dependent inhibition of MT 4 cell proliferation in vitro with apoptosis induction in the setting of the significant G2/M phase arrest (up to 70% of cells). While amitosine induced caspase-3 activation in MT-4 cells, the increase in the number of cells containing the active caspase 3 did not correlate with the increase of apoptotic cell percentage. Western blotting data revealed the accumulation of cytochrome c in cytosolic fraction of MT-4 cells within 6 h after treatment with 100 ?g/mL amitosine. To sum up, amitosine has been shown to possess strong antiproliferative and apoptosis-inducing activities in MT-4 cells in vitro, which seem to be mediated partially through caspase-dependent mitochondrial death pathways.
Key words: greater celandine, mixture of modified alkaloids, thiophosphamide, acute lymphoblastic leukemia, cell cycle, apoptosis, caspase-3.
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