RT Journal Article
T1 PKC Potentiates Tyrosine Kinase Inhibitors STI571 and Dasatinib Cytotoxic Effect
A1 Tobío Ageitos, Araceli
A1 Alfonso Rancaño, María Amparo
A1 Botana López, Luis Miguel
K1 HMC-1
K1 PKC
K1 c-kit
K1 STI571
K1 dasatinib
K1 PMA
AB 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-1560 and HMC-1560,816 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-1560 and HMC-1560,816 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.
PB The International Institute of Anticancer Research
YR 2014
FD 2014
LK https://hdl.handle.net/10347/38096
UL https://hdl.handle.net/10347/38096
LA eng
NO This research has received funding from the following FEDER cofunded-grants: From CDTI and Technological Funds, supported by Ministerio de Economía y Competitividad, AGL2012-40185CO2-01 and Consellería de Cultura, Educación e Ordenación Universitaria, GRC2013-016, and through Axencia Galega de Innovación, Spain, ITC-20133020 SINTOX, IN852A 2013/16-3 MYTIGAL. From CDTI under ISIP Programme, Spain, IDI20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA – Research Executive Agency (FP7/2007-2013) under grant agreement Nos. 265409 μAQUA, 315285 CIGUATOOLS and 312184 PHARMASEA. Araceli Tobío Ageitos is supported by a fellowship from Programa de Formación de Profesorado Universitario (AP2008/03904), Ministerio de Educación, Spain.
DS Minerva
RD 22 abr 2026