PKC potentiates tyrosine kinase inhibitors STI571 and dasatinib cytotoxic effect.
Year: 2014
Type: article
Abstract: AIM: The aim of the present study was to determine the relationship between the tyrosine kinase inhibitors, STI571 and dasatinib effects and protein kinase C (PKC) status in HMC-1(560) and HMC-1(560,816) cell lines. MATERIAL AND METHODS: Viability results were obtained by two different methods: MTT and a flow cytometry with Annexin V-FITC/PI double-staining protocol. The lipid-based transfection method was used to silence PKC. RESULTS: Long-term PKC activation induces apoptosis in both HMC-1 cell lines. Moreover, PKC activation potentiates STI571 and dasatinib cytotoxic effects in HMC-1(560) and HMC-1(560,816) cells, respectively, by increasing necrotic populations. To investigate this PKC effect, the role of PKCδ, an isoform intimately related with apoptotic cell death, was studied. The results obtained evidence that either STI571 or dasatinib apoptotic cell death are PKCδ-dependent. Particularly, STI571 showed less dependence to PKCδ than dasatinib. CONCLUSION: PKCδ modulation is essential and determines mastocytosis treatment effectiveness, since STI571 and dasatinib effects are PKCδ-dependent.
Source: PubMed
Authors: Araceli Tobío, Amparo Alfonso, Luis M Botana
Institution: Universidade de Santiago de Compostela
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2406427196