Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis = ARPC2 저해제인 벤프로페린의 암 전이 효과

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Title
Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis = ARPC2 저해제인 벤프로페린의 암 전이 효과
Author(s)
Yae Jin Yoon; Young-Min Han; Jiyeon Choi; Yu Jin Lee; Jieun Yun; Su-Kyung Lee; Chang Woo LeeJong Soon KangSeung-Wook ChiJeong Hee MoonSangku LeeDong Cho HanByoung-Mog Kwon
Bibliographic Citation
Biochemical Pharmacology, vol. 163, no. 1, pp. 46-59
Publication Year
2019
Abstract
Metastasis is the leading cause of cancer mortality and cancer cell migration is an essential stage of metastasis. We identified benproperine (Benp, a clinically used antitussive drug) as an inhibitor of cancer cell migration and an anti-metastatic agent. Benp selectively inhibited cancer cell migration and invasion, which also suppressed metastasis of cancer cells in animal models. Actin-related protein 2/3 complex subunit 2 (ARPC2) was identified as a molecular target of Benp by affinity column chromatography with Benp-tagged Sepharose beads. Benp bound directly to ARPC2 in cells, which was validated by pull-down assay using Benp-biotin and label-free biochemical methods such as the drug affinity responsive target stability (DARTS) and cellular thermal shift assay (CETSA). Benp inhibited Arp2/3 function, showing disruption of lamellipodial structure and inhibition of actin polymerization. Unlike Arp2/3 inhibitors, Benp selectively inhibited the migration of cancer cells but not normal cells. ARPC2-knockdown cancer cells showed defective cell migration and suppressed metastasis in an animal model. Therefore, ARPC2 is a potential target for anti-metastatic therapy, and Benp has the clinical potential to block metastasis. Furthermore, Benp is a useful agent for studying the functions of the Arp2/3 complex in cancer cell migration and metastasis.
Keyword
ARPC2Arp2/3 complexBenproperineDrug repurposingMetastasis
ISSN
0006-2952
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bcp.2019.01.017
Type
Article
Appears in Collections:
Division of Biomedical Research > Genome Editing Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
Division of Biomedical Research > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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