Limits...
Tocilizumab unmasks a stage-dependent interleukin-6 component in statin-induced apoptosis of metastatic melanoma cells.

Minichsdorfer C, Wasinger C, Sieczkowski E, Atil B, Hohenegger M - Melanoma Res. (2015)

Bottom Line: The effects of IL-6 were measured by western blots for STAT3 and Bcl-2 family proteins.This proapoptotic effect of IL-6 might be explained by a downregulation of Bcl-XL, observed only in WM35 cells.These results confirm that simvastatin facilitates apoptosis in combination with IL-6.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Oncology, Medicine I bCenter for Physiology and Pharmacology, Comprehensive Cancer Center, Institute of Pharmacology cDepartment of Neurology, Medical University of Vienna, Vienna, Austria.

No MeSH data available.


Related in: MedlinePlus

Interleukin (IL)-6 sensitizes WM35 melanoma cells for simvastatin-induced apoptosis, but not 518A2 and A375 cells. WM35 (a, b), 518A2, and A375 (c, d) cells were incubated in the absence (CTL) and presence of IL-6 (20 ng/ml) and the indicated concentrations of simvastatin (Sim) for 48 h. The cells were double stained with propidium iodide and Annexin V for quantification by FACS analysis in the upper panels (a, c). Three such experiments were collected for concentration–response curves (b, d). Statistical significance versus the corresponding simvastatin concentration: *P<0.05; ***P<0.001; n=3.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4492793&req=5

Figure 3: Interleukin (IL)-6 sensitizes WM35 melanoma cells for simvastatin-induced apoptosis, but not 518A2 and A375 cells. WM35 (a, b), 518A2, and A375 (c, d) cells were incubated in the absence (CTL) and presence of IL-6 (20 ng/ml) and the indicated concentrations of simvastatin (Sim) for 48 h. The cells were double stained with propidium iodide and Annexin V for quantification by FACS analysis in the upper panels (a, c). Three such experiments were collected for concentration–response curves (b, d). Statistical significance versus the corresponding simvastatin concentration: *P<0.05; ***P<0.001; n=3.

Mentions: Metastatic melanoma cells are sensitive to statin-induced apoptosis 13. We have therefore also investigated WM35 cells from the radial growth phase of melanoma for simvastatin-induced apoptosis by FACS analysis using Annexin V and propidium iodide double staining (Fig. 3). Only concentrations exceeding 10 μmol/l simvastatin were capable of significantly inducing apoptosis in WM35 cells, whereas this effect has already been observed at 1 μmol/l simvastatin in 518A2 and A375 cells. However, in WM35 cells, coincubation with IL-6 shifted the concentration–response curve significantly to the left and no effect was observed in 518A2 and A375 cells (Fig. 3b and d).


Tocilizumab unmasks a stage-dependent interleukin-6 component in statin-induced apoptosis of metastatic melanoma cells.

Minichsdorfer C, Wasinger C, Sieczkowski E, Atil B, Hohenegger M - Melanoma Res. (2015)

Interleukin (IL)-6 sensitizes WM35 melanoma cells for simvastatin-induced apoptosis, but not 518A2 and A375 cells. WM35 (a, b), 518A2, and A375 (c, d) cells were incubated in the absence (CTL) and presence of IL-6 (20 ng/ml) and the indicated concentrations of simvastatin (Sim) for 48 h. The cells were double stained with propidium iodide and Annexin V for quantification by FACS analysis in the upper panels (a, c). Three such experiments were collected for concentration–response curves (b, d). Statistical significance versus the corresponding simvastatin concentration: *P<0.05; ***P<0.001; n=3.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492793&req=5

Figure 3: Interleukin (IL)-6 sensitizes WM35 melanoma cells for simvastatin-induced apoptosis, but not 518A2 and A375 cells. WM35 (a, b), 518A2, and A375 (c, d) cells were incubated in the absence (CTL) and presence of IL-6 (20 ng/ml) and the indicated concentrations of simvastatin (Sim) for 48 h. The cells were double stained with propidium iodide and Annexin V for quantification by FACS analysis in the upper panels (a, c). Three such experiments were collected for concentration–response curves (b, d). Statistical significance versus the corresponding simvastatin concentration: *P<0.05; ***P<0.001; n=3.
Mentions: Metastatic melanoma cells are sensitive to statin-induced apoptosis 13. We have therefore also investigated WM35 cells from the radial growth phase of melanoma for simvastatin-induced apoptosis by FACS analysis using Annexin V and propidium iodide double staining (Fig. 3). Only concentrations exceeding 10 μmol/l simvastatin were capable of significantly inducing apoptosis in WM35 cells, whereas this effect has already been observed at 1 μmol/l simvastatin in 518A2 and A375 cells. However, in WM35 cells, coincubation with IL-6 shifted the concentration–response curve significantly to the left and no effect was observed in 518A2 and A375 cells (Fig. 3b and d).

Bottom Line: The effects of IL-6 were measured by western blots for STAT3 and Bcl-2 family proteins.This proapoptotic effect of IL-6 might be explained by a downregulation of Bcl-XL, observed only in WM35 cells.These results confirm that simvastatin facilitates apoptosis in combination with IL-6.

View Article: PubMed Central - PubMed

Affiliation: aDepartment of Oncology, Medicine I bCenter for Physiology and Pharmacology, Comprehensive Cancer Center, Institute of Pharmacology cDepartment of Neurology, Medical University of Vienna, Vienna, Austria.

No MeSH data available.


Related in: MedlinePlus