2. Academic Validation
  3. Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis

Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis

  • Biochem Pharmacol. 2019 May;163:46-59. doi: 10.1016/j.bcp.2019.01.017.
Yae Jin Yoon 1,  Young-Min Han 1,  Jiyeon Choi 2,  Yu-Jin Lee 1,  Jieun Yun 1,  Su-Kyung Lee 1,  Chang Woo Lee 1,  Jong Soon Kang 1,  Seung-Wook Chi 3,  Jeong Hee Moon 1,  Sangku Lee 1,  Dong Cho Han 4,  Byoung-Mog Kwon 5
Affiliations

Affiliations

  • 1 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon 34141, Republic of Korea.
  • 2 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon 34141, Republic of Korea; Department of Biology, Chungnam National University, Daejeon 34134, Republic of Korea.
  • 3 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon 34141, Republic of Korea; Korea University of Science and Technology in Korea, Daejeon, Republic of Korea.
  • 4 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon 34141, Republic of Korea; Korea University of Science and Technology in Korea, Daejeon, Republic of Korea. Electronic address: dchan@kribb.re.kr.
  • 5 Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon 34141, Republic of Korea; Korea University of Science and Technology in Korea, Daejeon, Republic of Korea. Electronic address: kwonbm@kribb.re.kr.
PMID: 30710516 DOI: 10.1016/j.bcp.2019.01.017
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.

Keywords

ARPC2; Arp2/3 complex; Benproperine; Drug repurposing; Metastasis.

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