Screening the toxic potential of Cylindrospermopsis raciborskii strains isolated from Lake Balaton, Hungary.
Geiparvarin, a natural compound isolated from the leaves of Geijera parviflora, inhibits the growth of various tumor cell lines with a mode of action which may be attributed to its anti-microtubular activity. Our previous findings indicated that geiparvarin is able to inhibit the in vitro polymerization of tubulin and to derange the microtubular network in fibroblasts more effectively in the presence of paclitaxel. To further explore its biological activity here we have studied the effects exerted on the other components of the cytoskeleton by geiparvarin and two derivatives obtained by conjugating the 3(2H)-furanone ring of geiparvarin with diethylstilbestrol (DES). Firstly, observations by electron microscopy confirmed anti-microtubular properties, a near-total absence of microtubules is detected when tubulin is incubated with drugs in the presence of paclitaxel, whereas microtubule formation is not inhibited by drugs when assembly is induced by guanosine 5'-triphosphate (GTP). Immunofluorescence assays demonstrated that geiparvarin and DES act in a vinblastine-like fashion, causing a marked depletion of intermediate filaments while the network of microfilaments is not affected. Both the conjugates alter the 'stress fibers' organization of actin and disrupt the vimentin pattern; generally they derange cytoskeleton more markedly than the parent compounds. The cell growth inhibiting effects of geiparvarin and derivatives are dose-dependent; they vary according to the cell line used, when compounds were administered either alone or simultaneously with paclitaxel. Unlike other anti-microtubule agents, they do not exhibit cell-cycle compartment specificity and do not influence thymidine uptake in the cell.