[Comparative effects of flavonoids on cell cycle passage and apoptosis induction in human acute lymphoblastic leukemia MT-4 cells].

In the present study, 8 flavonoids of three major flavonoid subgroups, namely flavones, flavonols and flavanones were tested for their cytotoxic and apoptogenic effects in human acute lymphoblastic leukemia MT-4 cells in vitro. Apoptotic cells were identified by DNA flow cytometric analysis. The effects of the flavonoids on the cell cycle patterns and activation of caspase-3 were also examined. Among the flavonoids tested, 7,8-benzoflavone, flavone, quercetin, chrysin, and galangine were shown to be effective apoptosis inducers. At concentrations corresponding to ED50, the flavonoids mentioned above exerted varying degrees of caspase-3 activation in MT-4 cells. The flavonoid-treated cells demonstrated different cell cycle profiles with accumulation in either G0/G1 (flavone, morin) or G2/M (7,8-benzoflavone, naringenin, quercetin, apigenin) phase. The induction of apoptosis did not correlate with phase-specific effects of flavonoid assayed. The relationship between chemical structure and apoptogenic activity of flavonoids tested is discussed.

[Modified alkaloids from Chelidonium majus L. induce G2/M arrest, caspase-3 activation, and apoptosis in human acute lymphoblastic leukemia MT-4 cells].

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 microg/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 microg/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.

[Elevated level of TGF-alpha in the mucosa of small intestine of the rat following massive small bowel resection]. / Pidvyshchennia vmistu transformuiuochogo faktora rostu typu alpha v epiteliï tonkogo kyshechnyka shchuriv pislia rezektsiï iogo bil'shoï chastyny.

This study was performed to determine the changes in TGF-alpha production during compensatory regeneration of small intestine. For this purpose rats underwent either 70% small bowel resection or sham operation. Levels of TGF-alpha production were evaluated by radioreceptor assay and Western blotting. When compared with sham operation, small bowel resection resulted in threefold increase in the production of TGF-alpha at postoperative day 3. Possible mechanisms of TGF-alpha involvement in intestinal adaptation following massive small bowel resection are discussed.