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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 production and signaling in human melanoma cells of different leasional stages. (a) Human melanoma cells 518A2, A375, and WM35 were cultured in serum-free medium for 48 h and analyzed for IL-6 levels with ELISA. Bars and errors indicate the mean±SD. (b) Serum starved human melanoma cells 518A2, A375, and WM35 were exposed to 20 ng/ml IL-6 for the indicated time points. Western blots show phosphorylated STAT3 (p-STAT3), which is compared with total STAT3 as a loading control.
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Figure 1: Interleukin (IL)-6 production and signaling in human melanoma cells of different leasional stages. (a) Human melanoma cells 518A2, A375, and WM35 were cultured in serum-free medium for 48 h and analyzed for IL-6 levels with ELISA. Bars and errors indicate the mean±SD. (b) Serum starved human melanoma cells 518A2, A375, and WM35 were exposed to 20 ng/ml IL-6 for the indicated time points. Western blots show phosphorylated STAT3 (p-STAT3), which is compared with total STAT3 as a loading control.

Mentions: Secretion of IL-6 has long been confirmed for murine and human melanoma cells 7,8. However, high levels of IL-6 have been found in late-stage melanoma correlated with a poor prognosis 23,24. We have therefore compared and characterized human early-stage WM35 melanoma cells with metastatic 518A2 and A375 cells. The metastatic melanoma cell lines secrete high amounts of IL-6 (121.4±39.9 pg/ml A375 cells; 540±169 pg/ml 518A2 cells) (Fig. 1). Conversely, WM35 cells secreted significantly less IL-6 (27.9±6.9 pg/ml). This latter concentration is very close to that published by Molnar et al. 23 for these cells.


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 production and signaling in human melanoma cells of different leasional stages. (a) Human melanoma cells 518A2, A375, and WM35 were cultured in serum-free medium for 48 h and analyzed for IL-6 levels with ELISA. Bars and errors indicate the mean±SD. (b) Serum starved human melanoma cells 518A2, A375, and WM35 were exposed to 20 ng/ml IL-6 for the indicated time points. Western blots show phosphorylated STAT3 (p-STAT3), which is compared with total STAT3 as a loading control.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Interleukin (IL)-6 production and signaling in human melanoma cells of different leasional stages. (a) Human melanoma cells 518A2, A375, and WM35 were cultured in serum-free medium for 48 h and analyzed for IL-6 levels with ELISA. Bars and errors indicate the mean±SD. (b) Serum starved human melanoma cells 518A2, A375, and WM35 were exposed to 20 ng/ml IL-6 for the indicated time points. Western blots show phosphorylated STAT3 (p-STAT3), which is compared with total STAT3 as a loading control.
Mentions: Secretion of IL-6 has long been confirmed for murine and human melanoma cells 7,8. However, high levels of IL-6 have been found in late-stage melanoma correlated with a poor prognosis 23,24. We have therefore compared and characterized human early-stage WM35 melanoma cells with metastatic 518A2 and A375 cells. The metastatic melanoma cell lines secrete high amounts of IL-6 (121.4±39.9 pg/ml A375 cells; 540±169 pg/ml 518A2 cells) (Fig. 1). Conversely, WM35 cells secreted significantly less IL-6 (27.9±6.9 pg/ml). This latter concentration is very close to that published by Molnar et al. 23 for these cells.

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