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We studied cytotoxic activity of new tetranitrosyl NO-generating binuclear iron-sulfur [Fe-S] complexes containing different ligands in the molecule against tumor cells in vitro. Cytotoxic activity of the most active complex with cysteamine (CysAm) was compared with that of antitumor drug cisplatin. Caspase activation and morphological changes in cells were visualized by fluorescence microscopy. Fluorescence of active caspases 3 and 7 and changes in nuclear DNA in cells in the presence of CyAm were detected by using fluorochrome-labeled inhibitor of caspases (FLICA) and Hoechst and propidium iodide reagents. Similar cytotoxic activities of CyAm and cisplatin were demonstrated in various human tumor cell lines of different histogenesis. Therefore, a new class of NO-donating [Fe-S] complexes can provide the base of potential drugs for chemotherapy with a new mechanism of action.

We studied cytotoxic activity of a new NO-releasing tetranitrosyl binuclear iron complex with cysteamine (CysAm) for human tumor cells, the relationship between the expression of O6-methylguanine-DNA methyltransferase (MGMT) and cell sensitivity to CysAm, and apoptosis-inducing capacity of this preparation. It was found that histogenetically different cell lines are characterized by different sensitivity to CysAm, and this parameter correlated with the basal level of MGMT. CysAm induced apoptosis via activation of caspases 3 and 7. These data suggest that CysAm can be considered as a potential antitumor agent, but definitive conclusions can be made after preclinical trials.

Here we present antiestrogenic effects of Knotolan, a new dietary lignan from Abies sibirica raw material. Knotolan abolished growth-stimulating effects of 17β-estradiol on hormone-dependent MCF-7 cells.

We studied the ability of lymphokine-activated killer cells to lyse A549 human non-small cell lung cancer cells after preincubation with cisplatin. Lymphokine-activated killer cells obtained after incubation of human blood lymphocytes with interleukin-2 were characterized by high expression of natural killer cell antigens and activation molecules. Lymphokine-activated killer cells produced potent cytotoxic effect on intact A549 cells and lysed tumor cells survived after treatment with cisplatin in concentrations of IC50 and IC30. Cisplatin in noncytotoxic concentrations did not increase lytic activity of lymphokine-activated killer cells.

We compared cytotoxic activity of blood mononuclear leukocytes from healthy donors and lymphokine-activated killer cells generated from them towards tumor and normal cells. Lymphokine-activated killer cells exhibited higher (in comparison with blood mononuclear leukocytes) killer activity towards tumor cells. Lymphokine-activated cells and mononuclear leukocytes had no lytic effect on non-transformed eukaryotic cells. Hence, we demonstrated selective cytotoxic activity of effector cells (lymphokine-activated killers) towards tumor cells of different origin (but not normal cells).