Our data reveal a dual mode of action of STF-31, serving either as a NAMPT or as a GLUT inhibitor, whereby the latter seems to be apparent only at higher STF-31 concentrations. The molecular basis of such a dual function and its appearance in compounds previously designated as NAMPT-specific inhibitors requires further investigation.

Cultivation of A549 non-small-cell lung carcinoma (NSCLC) cells in the presence of staurosporine (SSP) leads to a reduction or a lack of proliferation in a concentration-dependent manner. This inhibition of proliferation is accompanied by the generation of polyploid giant cancer cells (PGCCs) that are characterized by cell flattening, increased cell size, polyploidy, and polynucleation as determined by crystal violet staining, BrdU and DiI labelling, and flow cytometry as well as video time-lapse analysis. Continuous SSP treatment of A549 cells can preserve PGCCs for at least two months in a resting state. Upon removal of SSP, A549 PGCCs restart to divide and exhibit a proliferation pattern and cellular morphology indistinguishable from cells where PGCCs originally derived from. Thus, SSP-treated A549 cells represent a simple and reliable experimental model for the reversible generation of PGCCs and their subsequent experimental analysis.

Our data indicate that collective migration enables tumor cells to cross otherwise unfavourable substrate areas. This capacity seems to be independent of intercellular communication via gap junctions, whereas Rac1-dependent intracellular signalling seems to be essential.

A major challenge in tumor therapy is the decrease or even the halting of cell proliferation and migration of cancerous cells. In the present study, we have analyzed the impact of a pharmacological blockade of the PI3K/Akt and MAPK/ERK1/2 signaling pathways on cell migration, proliferation and cell death in three human thyroid tumor cell lines that represent the main types of malignant thyroid carcinomas (B-CPAP, follicular; Cal-62, anaplastic; FTC-133, papillary thyroid carcinoma cells) and in which these pathways are constitutively activated. In general, pharmacological perturbation of PI3/Akt (application of MK-2206) and MEK/ERK1/2 (application of PD0325901 or U0126) signaling led to a cell line and drug-specific decrease in the proliferation and migration potential of thyroid carcinoma cells, although to a varying extent. However, one exception became apparent: in Cal-62 cells inhibition of the MEK/ERK1/2 module increased the migration rate up to 50%. This effect could be prevented by a simultaneous suppression of the PI3/Akt pathway, but also by application of the multiple kinase inhibitor sorafenib, a treatment that did not change the activation state of Akt. Thus, a pharmacological perturbation of canonical signaling pathways in thyroid carcinoma may induce drug-dependent yin-yang effects that are characterized by a simultaneous suppression of one (i.e., proliferation) and the activation of another (i.e., migration) cellular process. The appearance of such phenomena should be taken into account when therapy plans are established.

Background: Staurosporine-dependent single and collective cell migration patterns of breast carcinoma cells MDA-MB-231, MCF-7, and SK-BR-3 were analysed to characterise the presence of drug-dependent migration promoting and inhibiting yin-yang effects. Methods: Migration patterns of various breast cancer cells after staurosporine treatment were investigated using Western blot, cell toxicity assays, single and collective cell migration assays, and video time-lapse. Statistical analyses were performed with Kruskal–Wallis and Fligner–Killeen tests. Results: Application of staurosporine induced the migration of single MCF-7 cells but inhibited collective cell migration. With the exception of low-density SK-BR-3 cells, staurosporine induced the generation of immobile flattened giant cells. Video time-lapse analysis revealed that within the borderline of cell collectives, staurosporine reduced the velocity of individual MDA-MB-231 and SK-BR-3, but not of MCF-7 cells. In individual MCF-7 cells, mainly the directionality of migration became disturbed, which led to an increased migration rate parallel to the borderline, and hereby to an inhibition of the migration of the cell collective as a total. Moreover, the application of staurosporine led to a transient activation of ERK1/2 in all cell lines. Conclusion: Dependent on the context (single versus collective cells), a drug may induce opposite effects in the same cell line.