title: Synergism between PKCδ regulators hypericin and rottlerin enhances apoptosis in U87 MG glioma cells after light stimulation.
abstract: BACKGROUND
  Gliomas belong to the most infiltrative types of tumors. Photodynamic therapy (PDT) can be applied to regulate glioma cell proliferation. The inhibitors of PKCs (Protein Kinase C) 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Department of Biophysics, Faculty of Science, P. J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia.
authors.forename: Matus
authors.initials: M
authors.lastname: Misuth
authors.affiliation: Center for Interdisciplinary Biosciences, Faculty of Science, P.J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia.
authors.forename: Denis
authors.initials: D
authors.lastname: Horvath
authors.affiliation: Center for Interdisciplinary Biosciences, Faculty of Science, P.J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia.
authors.forename: Pavol
authors.initials: P
authors.lastname: Miskovsky
authors.affiliation: Center for Interdisciplinary Biosciences, Faculty of Science, P.J. Safarik University in Kosice, Jesenna 5, 041 54 Kosice, Slovakia. Electronic address: veronika.huntosova@upjs.sk.
authors.forename: Veronika
authors.initials: V
authors.lastname: Huntosova
mesh_terms: D000098:Acetophenones / Q000008:administration & dosage*; D020533:Angiogenesis Inhibitors; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001578:Benzopyrans / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008027:Light; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010778:Photochemotherapy / Q000379:methods; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage
chemical_list: D000098:Acetophenones; D020533:Angiogenesis Inhibitors; D000873:Anthracenes; D000970:Antineoplastic Agents; D001578:Benzopyrans; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin; C085746:rottlerin; D051745:Protein Kinase C-delta
keywords: Apoptosis; Bcl-2; Glioma cell; Hypericin; Photodynamic therapy; Rottlerin