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Searching for combination therapy by clustering methods: Stimulation of PKC in Golgi apparatus combined with hypericin induced PDT.

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Cancer cells metabolism is nowadays a very attractive target of anticancer treatments. This work focuses on protein kinase C (PKC) signaling in the U87 MG glioma. By means of western… Click to show full abstract

Cancer cells metabolism is nowadays a very attractive target of anticancer treatments. This work focuses on protein kinase C (PKC) signaling in the U87 MG glioma. By means of western blot, fluorescence and time-resolved fluorescence microscopy the correlations between the Golgi apparatus (GA), lysosomes and mitochondria were evaluated. The known regulators of PKC were applied to cancer cells. Phorbol myrastil acetate (PMA) was chosen as the activator of PKC. Gö6976, hypericin and rottlerin, the inhibitors of PKCα and PKCδ were selected as well. Stabilization, destabilization processes occurring in cells allow classification of observations into several groups. Multiple versions of hierarchical cluster analysis have been applied and similarities have been found between organelles and PKC regulators. The method identified GA as an extraordinary organelle whose functionality is significantly influenced by PKC regulators as well as oxidative stress. Therefore, the combination therapy has been designed according to the results of the cluster analysis. Furthermore, the efficacy of photodynamic therapy mediated by hypericin, and the consequent apoptosis, was significantly increased during the treatment. To our knowledge, this is the first demonstration of the effectiveness of the clustering in the given area.

Keywords: combination therapy; hypericin; golgi apparatus; therapy; pkc

Journal Title: Photodiagnosis and photodynamic therapy
Year Published: 2020

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