Type

Journal Article

Authors

Norma O'Donovan
Martin Clynes
John Crown
Alex J Eustace

Subjects

Biochemistry

Topics
antineoplastic agents humans thiazoles pyridines protein kinase inhibitors cell cycle blotting western focal adhesion protein tyrosine kinases dacarbazine cell line tumor temozolomide proto oncogene proteins pp60 c src cell movement pathology melanoma neoplasm invasiveness pharmacology drug screening assays antitumor drug synergism apoptosis pyrimidines drug effects dasatinib antagonists inhibitors receptor epha2 analogs derivatives cell proliferation benzenesulfonates sorafenib

Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines. (2008)

Abstract Metastatic melanoma is a highly chemotherapy resistant tumour. The use of newer targeted therapies alone and in combination with chemotherapy may offer new hope of improving response to treatment. Dasatinib, a multi-target kinase inhibitor, is currently approved for the treatment of chronic myeloid leukaemia and has shown promising results in preclinical studies in a number of solid tumours. We examined the effects of dasatinib on proliferation, chemo-sensitivity, cell cycle arrest, apoptosis, migration and invasion in human melanoma cell lines. Expression and activation of Src kinase, FAK and EphA2 were also examined in the melanoma cells. Dasatinib inhibited growth of three of the five melanoma cell lines. Comparison with sorafenib showed that in these three cell lines dasatinib inhibited growth at lower concentrations than sorafenib. Dasatinib in combination with the chemotherapy drug temozolomide showed greater efficacy than either drug alone. Dasatinib induced cell cycle arrest and apoptosis and significantly inhibited cell migration and invasion of melanoma cells. Dasatinib inhibition of proliferation was associated with reduced phosphorylation of Src kinase, while decreased phosphorylation of FAK was implicated in dasatinib-mediated inhibition of migration and invasion in melanoma cells. Dasatinib has both anti-proliferative and anti-invasive effects in melanoma cells and combined with chemotherapy may have clinical benefit in the treatment of malignant melanoma.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

Norma O'Donovan, Martin Clynes, John Crown, Alex J Eustace

Experts in our system

1
Norma O'Donovan
Dublin City University
Total Publications: 52
 
2
Martin Clynes
Dublin City University
Total Publications: 209
 
3
John Crown
Dublin City University
 
4
Alex J Eustace
Royal College of Surgeons in Ireland
Total Publications: 23