Synergism between PKCδ regulators hypericin and rottlerin enhances apoptosis in U87 MG glioma cells after light stimulation

Publication date: Available online 31 March 2017
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Matus Misuth, Denis Horvath, Pavol Miskovsky, Veronika Huntosova
BackgroundGliomas belong to the most infiltrative types of tumors. Photodynamic therapy (PDT) can be applied to regulate glioma cell proliferation. The inhibitors of PKCs are very promising drugs that can mediate glioma cells apoptosis in PDT. Hypericin is one of PKCs regulators, and thanks to its physicochemical properties it can be used in PDT. Rottlerin is also considered to be the PKCδ inhibitor. Its implementation in PDT may significantly influence glioma cells response to PDT.MethodsThe viability of U87 MG glioma cells in the presence of rottlerin and hypericin was assessed by MTT assay and flow cytometry in the absence and presence of light. The flow cytometric data were analyzed through Shannon entropy. The oxidative stress and immunocytochemistry of PKCδ and phosphorylated Bcl-2 (the regulators of apoptosis) were observed using fluorescence microscopy.ResultsA pretreatment of glioma cells with rottlerin before hypericin induced PDT led to significant increase in apoptosis accompanied by the decrease of intracellular oxidative stress and increase of phosphorylated Bcl-2 in the cytoplasm of U87 MG cells.ConclusionsIn conclusion, we assume that the synergism between rottlerin and hypericin leads firstly to activation of rescue mechanisms in the glioma cells, but finally this cooperation triggers apoptosis rather than necrosis.

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