The Role of Anti-apoptotic Protein kinase Ca in Response to Hypericin Photodynamic Therapy in U-87 MG Cells.

Photodiagnosis and photodynamic therapy

PubMedID: 24583280

Dzurov√° L, Petrovajova D, Nadova Z, Huntosova V, Miskovsky P, Stroffekova K. The Role of Anti-apoptotic Protein kinase Ca in Response to Hypericin Photodynamic Therapy in U-87 MG Cells. Photodiagnosis Photodyn Ther. 2014;.
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 PKCa in U87 MG cells. To follow up on our previous work, we investigated how HypPDT influences PKCa in U87 MG cells. Here, we show that majority of PKCa 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 PKCa distribution. HypPDT acute effect caused PKCa activation and translocation along the plasma membrane and partially in the nuclei. The prolonged effect of HypPDT, 5 and 24hrs post PDT, results in PKCa located predominantly in cytosol and nuclei. Moreover, we have shown that phosphorylated catalytically competent PKCa is critical for U87 glioma cell viability in response to HypPDT treatment.