title: Luteolin inhibits recruitment of monocytes and migration of Lewis lung carcinoma cells by suppressing chemokine (C-C motif) ligand 2 expression in tumor-associated macrophage.
abstract: Tumor-associated macrophages (TAMs) play pivotal roles in the progression of cancer. In order to investigate a novel candidate that inhibits the tumor-supporting M2-like phenotype of TAMs, a murine macrophage cell line RAW 264.7 cells were treated with interleukin (IL)-4. Luteolin inhibited phosphorylation of signal transducer and activator of transcription 6 (STAT6), a main downstream signal of IL-4, and reduced the expression of the M2-associated genes. In addition, Luminex multiplex analysis for secreted cytokines revealed that IL-4-enhanced secretion of chemokine (C-C motif) ligand 2 (CCL2) was reduced by luteolin treatment. IL-4-stimulated migration of monocyte, THP-1 cells, was inhibited by luteolin treatment and recovered by recombinant CCL2 supplement. Moreover, luteolin decreased migration of Lewis lung carcinoma cells in a CCL2-dependent manner. Given the important role of the TAM phenotype in the tumor microenvironment, inhibitory effect of luteolin on the monocyte recruitment and cancer migration via suppression of the TAM-secreted CCL2 may suggest a novel therapeutic approach to treat malignant tumors.
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chung
authors.affiliation: Department of Korean Medical Science, School of Korean Medicine and Healthy Aging Korean Medicine Research Center, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea. Electronic address: hagis@pusan.ac.kr.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology* / Q000503:physiopathology*; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D047311:Luteolin / Q000008:administration & dosage*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009361:Neoplasm Invasiveness; D000067996:RAW 264.7 Cells
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D047311:Luteolin
keywords: CCL2; IL-4; Luteolin; Migration; STAT6; TAMs