4 on apoptosis and cell cycle of leukemia Preconcentrated, purified MTDND. Treated to the mechanism by which four MTDND cell death Ren aufzukl Were, and untreated CYT997 cells from ATL Grunwald Giemsa-F Examined staining and May-histogram analysis of DNA flow cytometry. Treatment with 4 MTDND entered Born disruption of nuclear material of the cell, the formation of apoptotic K Body and conclude Lich confinement to cell death after 48 hours, and up regulation of proapoptotic proteins Lich 9th PARP cleavage, caspase 3 and caspase Additionally Tzlich showed DNA analysis by F Dyeing histrogram propidium iodide and flow cytometry after 24 hours after treatment, a dose- Independent increase in the proportion of Leuk Preconcentrated, purified S1T in the G2 / M cell cycle, and that a Erh Increase in the proportion of cells below in the G1 phase.
Similar results were obtained with four treatments MTDND oncoprotein of HTLV-1 imp T cells, the ATL, K3T and IL 2 dependent KaT01F Ngig obtained ATL cell line. Therefore resulted CYC116 Aurora Kinase inhibitor in the permeabilization and intracellular Re F Staining with monoclonal antibodies Rpern against phosphorylated cyclin B1 and CDK1 and secondary Ren color with the corresponding fluorescent-labeled antibody Body, a significant decrease in cyclin B1, and an increase in the phosphorylated inactive form of CDK1 after 48 hours, treatment with 4 MTDND. These data show that presents four MTDND its cytotoxic effect on leukemia Preconcentrated, purified pr Of apoptosis and induce the F Promotion of G2 / M arrest. 4 MTDND on multidrug-resistant cancer cells.
Due to the reason why resistance remains a big obstacle was in the clinical treatment of various cancers, the effect of 4 MTDND several multidrug-resistant cancer cell lines was also determined. The cell line is KBABCC1, carcinoma cells Epidemo Transfected F Stable ABCC1 cDNA was as KRN 633 sensitive to the cytotoxic effect of 4 MTDND its corresponding non-resistant cells, the team of professionals with an IC50 value KBWhite3 of 8.2 and 7.0 nM. In addition, IC 50 of 4 MTDND cancer cells and KB 3 1 KBABCC1 were about 20 times and 400 times lower and the IC50 of etoposide against the same cells. In Similar way K562/ABCG2 cells showed sensitivity to the cytotoxic effects of 4 MTDND with an IC50 of 8.2 nM, about 30 times lower than that of the chemotherapeutic agent mitoxantrone.
Pgp-expressing cell line KBG 2 was also sensitive to 4 MTDND, with an IC50 of 7.7 nM, 110 times lower than the IC50 of etoposide against the same cells. Remarkably, the IC 50 were tested by four to three MTDND multidrug-resistant cancer cell lines compared with the IC50 of 4 MTDND to non-resistant leukemia Preconcentrated, purified S1T. The four new cytotoxic agent MTDND is effective against several MDR cancer cell lines, and at doses well below etoposide or mitoxantrone. A new discussion cytotoxic agents, MTDND 4, was out of the Jama, a popular medicinal plant Hyptis verticillata Jacq, with cytotoxic effects on the induction of apoptosis in a variety of h Dermatological and h isolated Dermatological cancer cells Including Lich multidrug-resistant cell lines . This compound showed a wide therapeutic index, the cytotoxicity t to normal activated PBMC from a healthy donor, the 30 to 40 times h was Than they are on cancer cells. Cancer multidrug