Cytotoxicity of two derivatives of 3,6-bis(3-alkylguanidino)acridines (GNDAs; pentyl-and hexyl-GNDA) was determined against three cell lines: a murine immortalized fibroblast cell line NIH-3T3, a human ovarian carcinoma cell line A2780, and a human neuroblastoma cell line SH-SY5Y. We found out that these GNDAs were cytotoxic against A2780 and NIH-3T3 cells but they showed only a marginal cytotoxicity against neuroblastoma cells SH-SY5Y. To explain differences in cytotoxicity, intracellular distribution of GNDAs was monitored. GNDAs were accumulated in A2780 and NIH-3T3 cells in the nuclei (fluorescence microscopy). In contrast to these cell lines, in SH-SY5Y cells, GNDAs were localized outside of the nuclei, at the plasma membrane and surroundings, extending also to the cytosol. This distribution of GNDAs was confirmed by an ImageStream Flow Cytometer. Acetylcholinesterase (AChE) activity in the SH-SY5Y cells decreased upon incubation with GNDAs. Kinetic studies showed that GNDAs were able to inhibit AChE by the same mode as tacrine (9-amino-1,2,3,4-tetrahydroacridine), a known inhibitor of AChE. A low cytotocity of GNDAs against SH-SY5Y cells could be caused by their affinity to AChE (the enzyme is localized mainly at the plasma membrane). The interaction of GNDAs with AChE may affect their intracellular distribution and consequently the cytotoxicity.
The effect of 3-(benzyloxycarbonylmethyl)-2-benzothiazolinone (SM-550) on the growth parameters, cell division, and cell polymorphism of spruce callus cells (Picea abies L. Karst) was investigated. These results were compared with callus parameters grown on the medium supplemented with NAA. The highest concentration (1 mmol) of SM-550 stimulated the growth process, as well as cell division, shortened the lag-phase, and had a significant effect on cells polymorphism. Its effect was demonstrated especially on long-term culture (3 subcultures – 84 days). On the other hand, the highest stimulation of growth by SM-550 in 1 μmol concentration was determined only in the first subculture. SM-550 in the lowest concentration (1 nmol) used was completely unsuitable in the third subculture, the callus was necrotic and resembled to calli growing on the medium without growth hormones.
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