Biopolym. Cell. 2012; 28(2):121-128.
Structure and Function of Biopolymers
Study of molecular mechanisms of proapoptotic action of novel heterocyclic 4-thiazolidone derivatives
1Panchuk R. R., 2Chumak V. V., 2Fil' M. R., 3Havrylyuk D. Ya., 3Zimenkovsky B. S., 3Lesyk R. B., 1, 2Stoika R. S.
  1. Institute of Cell Biology, NAS of Ukraine
    14/16, Drahomanov Str., Lviv, Ukraine, 79005
  2. Ivan Franko National University of L'viv
    4, Hrushevskoho Str., Lviv, Ukraine, 79005
  3. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010


Aim. Mechanisms of induction of apoptosis signaling pathways in mammalian tumor cells treated by novel heterocyclic 4-thiazolidones with different side groups were studied. Methods. Annexin V/propidium iodide and DAPI (4',6-diamidino-2-phenylindole) staining of cells, Western-blot analysis of specific proteins. Results. 4-Thiazolidone derivatives of various structure possess similar cytotoxic activity in vitro (IC50 = 5 µM), and induce apoptosis in both leukemia (Jurkat, CCRF-CEM) and carcinoma (MCF-7, MDA-MD-231) cells. Western-blot analysis of the expression of several proteins of apoptosis signaling showed that the structure of lateral groups of 4-thiazolidones may directly affect biological activity of these proteins in leukemia cells. In particular, compounds Les-3120 (pyrazoline-substituted thiazolidinone) and Les-3166 (thiazolidinone-benzothiazole conjugate) induced receptor-mediated apoptosis in Jurkat T-leukemia cells. 4-Iminothiazolidinone Les-3372 caused mitochondrial type apoptosis, mediated by AIF protein. Conclusions. Structure-functional relationships between the presence of specific side groups in novel 4-thiazolidones and the signaling apoptotic pathways induced by these compounds have been established. The obtained results allow designing new, «hybrid» compounds which can simultaneously induce more than one apoptotic pathway in tumor cells.
Keywords: tumor cells, apoptosis, 4-thiazolidones, caspases, AIF, structure-functional relationships


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