Src family kinase targeting in head and neck tumor cells using SU6656, PP2 and dasatinib.

Abstract

BACKGROUND:

We have recently shown a frequent upregulation of Src-family kinases (SFK) in head and neck squamous cell carcinoma (HNSCC). Here we tested, if SFK targeting is effective especially in HNSCC cells with upregulated SFK signaling.

METHODS:

The impact of SFK inhibitors SU6656, PP2 and dasatinib on three HNSCC cell lines with different SFK activity levels was analyzed using proliferation and colony formation assays, Western blot and functional kinomics.

RESULTS:

Proliferation was blocked by all inhibitors in a micro-molar range. With respect to cell kill, dasatinib was most effective, while SU6656 showed moderate and PP2 minor effects. Cellular signaling was affected differently, with PP2 having no effect on SFK signaling while dasatinib probably has non-SFK specific effects. Only SU6656 showed clear SFK specific effects on signaling.

CONCLUSION:

The results demonstrate potential benefit of SFK inhibition in HNSCC but they also highlight challenges due to non-specificities of the different drugs.

• Authors: Anh Thu Vu, Lara Akingunsade, Konstantin Hoffer, Cordula Petersen, Christian Stephan Betz, Kai Rothkamm, Thorsten Rieckmann, Lara Bussmann, Malte Kriegs
• Journal: Head & neck (Head Neck) Vol. 45 Issue 1 Pg. 147-155 (01 2023) ISSN: 1097-0347 [Electronic] United States
• PMID: 36285353 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.

Chemical References

• Dasatinib
• src-Family Kinases
• Pyrimidines
• SU 6656
• Protein Kinase Inhibitors

Topics

• Humans
• Dasatinib (pharmacology)
• src-Family Kinases (metabolism)
• Pyrimidines (pharmacology)
• Head and Neck Neoplasms (drug therapy)
• Squamous Cell Carcinoma of Head and Neck (drug therapy)
• Protein Kinase Inhibitors (pharmacology)
• Cell Line, Tumor