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

Title
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
Authors
Kauser Siddiqui김건웅이동훈신혜련양은경이남택양범석
Keywords
Actinimycin D; DDR2; collagen; inhibitor; screening; insect cell
Issue Date
2009-01
Publisher
Biological & pharmaceutical bulletin
Citation
VOL 32, NO 1, 136-141
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/36098
ISSN
0918-6158
Appears in Collections:
KIST Publication > Article
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