title: Anti-rheumatic drug iguratimod (T-614) alleviates cancer-induced bone destruction via down-regulating interleukin-6 production in a nuclear factor-κB-dependent manner.
abstract: Cytokines are believed to be involved in a "vicious circle" of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose (30 μg/mL) iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.
authors.affiliation: Cancer Center, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Cancer Center, Huazhong University of Science and Technology, Wuhan, 430030, China. dy0711@gmail.com.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Ye
authors.affiliation: Cancer Center, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ying-Xing
authors.initials: YX
authors.lastname: Wu
authors.affiliation: Cancer Center, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Bang-Yan
authors.initials: BY
authors.lastname: Wang
authors.affiliation: Cancer Center, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Peng
authors.affiliation: Cancer Center, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D001862:Bone Resorption / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D063646:Carcinogenesis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D051381:Rats; D013449:Sulfonamides / Q000008:administration & dosage*; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002867:Chromones; D015850:Interleukin-6; C498143:RELA protein, human; D013449:Sulfonamides; D051996:Transcription Factor RelA; C519076:iguratimod
keywords: bone destruction; bone metastasis; cytokines; iguratimod; nuclear factor-κB