Actinomycin D Identified as an Inhibitor of Discoidin Domain Receptor 2 Interaction with Collagen through an Insect Cell Based Screening of a Drug Compound Library
- Actinomycin D Identified as an Inhibitor of Discoidin Domain Receptor 2 Interaction with Collagen through an Insect Cell Based Screening of a Drug Compound Library
- Kauser Siddiqui; 김건웅; 이동훈; 신혜련; 양은경; 이남택; 양범석
- Actinimycin D; DDR2; collagen; inhibitor; screening; insect cell
- Issue Date
- Biological & pharmaceutical bulletin
- VOL 32, NO 1, 136-141
- Discoidin domain receptors belong to the cell surface receptor tyrosine kinase family and recognize collagens
for their activating ligands. They have been implicated for cell growth and migration and their elevated expressions
were observed in various human cancers. When we expressed human Discoidin domain receptor 2
(DDR2) in insect cells, the protein was targeted properly into the cell membrane and this could enforce the cells
to adhere on culture plate coated with type I collagen. By taking advantage of this, we established a novel insect
cell based screening protocol to identify chemicals which inhibit the interaction between DDR2 and collagen. We
screened a drug-compound library to select an anti-cancer drug, actinomycin D, as the inhibitory compound.
Actinomycin D prevented the activation of DDR2 by type I collagen in human embryonic kidney 293 cells with
an IC50 value of 9mM, while it did not interfere with the activation of other receptor tyrosine kinases by their
ligands. In conclusion we identified a new biological function of actinomycin D and the insect cell based
method provides a useful protocol for screening inhibitors against the association of DDR2 with collagen.
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