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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 downregulates the Bcl-2 family member, Bcl-XL in WM35 melanoma cells. Melanoma cells A375, 518A2, and WM35 were kept under serum-free conditions in the absence [control (CTL)] and presence of 20 ng/ml IL-6 for 48 h. (a) Bcl-2 family members, Bcl-XL, Bax, Bcl-2, and Bak were visualized using α-tubulin as a loading control. (b–e) Three independent experiments were analyzed for intensity and presented as mean±SEM (n=3). Statistical significance versus control: *P<0.05; **P<0.01; ***P<0.001; NS, not significant.
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Figure 5: Interleukin (IL)-6 downregulates the Bcl-2 family member, Bcl-XL in WM35 melanoma cells. Melanoma cells A375, 518A2, and WM35 were kept under serum-free conditions in the absence [control (CTL)] and presence of 20 ng/ml IL-6 for 48 h. (a) Bcl-2 family members, Bcl-XL, Bax, Bcl-2, and Bak were visualized using α-tubulin as a loading control. (b–e) Three independent experiments were analyzed for intensity and presented as mean±SEM (n=3). Statistical significance versus control: *P<0.05; **P<0.01; ***P<0.001; NS, not significant.

Mentions: We have previously shown that the proapoptotic effects of statins are triggered by translocation of the Bcl-2 homology (BH) domain member Bax into the mitochondrial membrane 15. As the proapoptotic Bcl-2 members are counterbalanced by binding to antiapoptotic Bcl-2 members, we investigated these proteins in the absence and presence of IL-6 (Fig. 5). In the metastatic melanoma cells, the levels of proapoptotic Bak and Bax and antiapoptotic Bcl-2 and Bcl-XL showed different responses upon IL-6 treatment. Bcl-XL was clearly decreased in WM35 cells in the presence of IL-6. In addition, the amount of Bcl-2 was decreased, whereas the level of proapototic proteins remained unchanged (Fig. 5).


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 downregulates the Bcl-2 family member, Bcl-XL in WM35 melanoma cells. Melanoma cells A375, 518A2, and WM35 were kept under serum-free conditions in the absence [control (CTL)] and presence of 20 ng/ml IL-6 for 48 h. (a) Bcl-2 family members, Bcl-XL, Bax, Bcl-2, and Bak were visualized using α-tubulin as a loading control. (b–e) Three independent experiments were analyzed for intensity and presented as mean±SEM (n=3). Statistical significance versus control: *P<0.05; **P<0.01; ***P<0.001; NS, not significant.
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Related In: Results  -  Collection

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Show All Figures
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Figure 5: Interleukin (IL)-6 downregulates the Bcl-2 family member, Bcl-XL in WM35 melanoma cells. Melanoma cells A375, 518A2, and WM35 were kept under serum-free conditions in the absence [control (CTL)] and presence of 20 ng/ml IL-6 for 48 h. (a) Bcl-2 family members, Bcl-XL, Bax, Bcl-2, and Bak were visualized using α-tubulin as a loading control. (b–e) Three independent experiments were analyzed for intensity and presented as mean±SEM (n=3). Statistical significance versus control: *P<0.05; **P<0.01; ***P<0.001; NS, not significant.
Mentions: We have previously shown that the proapoptotic effects of statins are triggered by translocation of the Bcl-2 homology (BH) domain member Bax into the mitochondrial membrane 15. As the proapoptotic Bcl-2 members are counterbalanced by binding to antiapoptotic Bcl-2 members, we investigated these proteins in the absence and presence of IL-6 (Fig. 5). In the metastatic melanoma cells, the levels of proapoptotic Bak and Bax and antiapoptotic Bcl-2 and Bcl-XL showed different responses upon IL-6 treatment. Bcl-XL was clearly decreased in WM35 cells in the presence of IL-6. In addition, the amount of Bcl-2 was decreased, whereas the level of proapototic proteins remained unchanged (Fig. 5).

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