It should be emphasized that compounds ZKKs induced apoptosis in the K-562 cells derived
from a woman with chronic myeloid leukemia (CML) in blast crisis (Lozzio and Lozzio, 1975; McGahon et al., 1994). The K-562 cells carry the Philadelphia (Ph) chromosome (Lozzio and Lozzio, 1975). The result of this chromosomal translocation is formation of the oncogenic Bcr-Abl fusion gene that is constitutively active. The product of the Bcr-Abl gene is a protein Selleck JPH203 with tyrosine kinase activity. Bcr-Abl-expressing leukemic cells show resistance to apoptosis induced by chemotherapeutic drugs (McGahon et al., 1994), which seems to be related to overexpression of the antiapoptotic protein Bcl-xL (Horita et al., 2000). In general, K562 cells are highly resistant to multiple anticancer agents and easily transform to 17DMAG drug-resistant lines during treatment by novel drugs (McGahon et al., 1994; Bedi et al., 1995; Amarante-Mendes et al., 1998). Concluding remarks Our results suggest that N-substituted selleck screening library pentabromobenzylisothioureas might be promising anticancer agents. The study on anticancer activity of this compound class in solid tumors is in progress, and further investigations are needed to evaluate their clinical potential. Acknowledgment
This study was supported by the Ministry of Science and Higher Education (Poland) grants: PBZ-MIN 014/P05/2004 IMP dehydrogenase and N N209 371439. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References Amarante-Mendes GP, Naekyung KC, Liu L, Huang Y, Perkins CL, Green DR, Bhalla K (1998) Bcr-Abl exerts its anti-apoptotic effect against diverse apoptotic stimuli through blockage of mitochondrial release of cytochrom C and activation of caspase-3. Blood 91:1700–1705PubMed Bedi A, Barber JP, Bedi GC, El-Deiry WS, Sidransky D,
Vala MS, Akhtar AJ, Hilton J, Jones RJ (1995) BCR-ABL-mediated inhibition of apoptosis with delay of G2M transition after DNA damage: a mechanism of resistance to multiple anticancer agents. Blood 86:1148–1158PubMed Carmona A, Gonzalez-Cadavid NF (1978) Comparative effect of a family of substituted thiopseudoureas on protein synthesis by rat liver and Walker carcinoma ribosomes. Chem Biol Interact 22:309–327PubMedCrossRef Castano T, Encinas A, Perez C, Castro A, Campillo NE, Gil C (2008) Design, syntheses, and evaluation of potential inhibitors of nitric oxide synthase. Bioorg Med Chem 16:6193–6206PubMedCrossRef Garvey EP, Oplinger JA, Tanaoury GJ, Sherman PA, Fowler M, Marshall S, Harmon MF, Paith JE, Furfine ES (1994) Potent and selective inhibition of human nitric oxide synthases. Inhibition by non-amino acid isothioureas.