The role of anti-apoptotic protein kinase Cα in response to hypericin photodynamic therapy in U-87 MG cells

Abstract

Hypericin photodynamic therapy (HypPDT) has been found to be an efficient inducer of cell death. However, there are indications that HypPDT also activates rescuing pathways. Cell responses to HypPDT are highly dependent on the Hyp intracellular localization and accumulation. We have shown previously that in U87 MG cells Hyp localizes mostly in ER and partially in mitochondria, lysosomes and Golgi, and that HypPDT resulted primarily in apoptosis via the mitochondrial apoptotic pathway. We have also shown that Hyp co-localizes and interacts with anti-apoptotic PKCα in U87 MG cells. To follow up on our previous work, we investigated how HypPDT influences PKCα in U87 MG cells. Here, we show that majority of PKCα present in U87 MG cells is already in a catalytically competent form phosphorylated at Thr638, and it is a likely Bcl2 kinase. The presence of Hyp itself does not affect PKCα distribution. HypPDT acute effect caused PKCα activation and translocation along the plasma membrane and partially in the nuclei. The prolonged effect of HypPDT, 5 and 24h post PDT, results in PKCα located predominantly in cytosol and nuclei. Moreover, we have shown that phosphorylated catalytically competent PKCα is critical for U87 glioma cell viability in response to HypPDT treatment.