title: Onbaekwon Suppresses Colon Cancer Cell Invasion by Inhibiting Expression of the CXC Chemokine Receptor 4.
abstract: Cysteine X cysteine (CXC) chemokine receptor 4 (CXCR4) and C-X-C motif chemokine 12 (CXCL12) were originally identified as chemoattractants between immune cells and sites of inflammation. Since studies have validated an increased level of CXCL12 and its receptor in patients with colorectal cancers, CXCL12/CXCR4 axis has been considered as a valuable marker of cancer metastasis. Therefore, identification of CXCR4 inhibitors has great potential to abrogate tumor metastasis. Onbaekwon (OBW) is a complex herbal formula that is derived from the literature of traditional Korean medicine Dongeuibogam. In this study, we demonstrated that OBW suppressed CXCR4 expression in various cancer cell types in a concentration- and time-dependent manner. Both proteasomal and lysosomal inhibitors had no effect to prevent the OBW-induced suppression of CXCR4, suggesting that the inhibitory effect of OBW was not due to proteolytic degradation but occurred at the transcriptional level. Electrophoretic mobility shift assay further confirmed that OBW could block endogenous activation of nuclear factor kappa B, a key transcription factor that regulates the expression of CXCR4 in colon cancer cells. Consistent with the aforementioned molecular basis, OBW abolished cell invasion induced by CXCL12 in colon cancer cells. Together, our results suggest that OBW, as a novel inhibitor of CXCR4, could be a promising therapeutic agent contributing to cancer treatment.
authors.affiliation: 1 Keimyung University, Daegu, South Korea.
authors.forename: Buyun
authors.initials: B
authors.lastname: Kim
authors.affiliation: 1 Keimyung University, Daegu, South Korea.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Yoon
authors.affiliation: 2 Kyung Hee University Hospital at Gangdong, Seoul, Korea.
authors.forename: Seong Woo
authors.initials: SW
authors.lastname: Yoon
authors.affiliation: 1 Keimyung University, Daegu, South Korea.
authors.forename: Byoungduck
authors.initials: B
authors.lastname: Park
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D055670:Medicine, Korean Traditional / Q000379:methods; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D016328:NF-kappa B; D010936:Plant Extracts; D019718:Receptors, CXCR4
keywords: CXCL12; CXCR4; colon cancer; invasion; metastasis; onbaekwon