title: Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast caner cells and osteoclasts.
abstract: Bone is the most common site of distant relapse in breast cancer, leading to severe complications which dramatically affect the patients' quality of life. It is believed that the crosstalk between metastatic breast cancer cells and osteoclasts is critical for breast cancer-induced osteolysis. In this study, the effects of dihydroartemisinin (DHA) on osteoclast formation, bone resorption, osteoblast differentiation and mineralization were initially assessed in vitro, followed by further investigation in a titanium-particle-induced osteolysis model in vivo. Based on the proved inhibitory effect of DHA on osteolysis, DHA was further applied to MDA-MB-231 breast cancer-induced mouse osteolysis model, with the underlying molecular mechanisms further investigated. Here, we verified for the first time that DHA suppressed osteoclast differentiation, F-actin ring formation and bone resorption through suppressing AKT/SRC pathways, leading to the preventive effect of DHA on titanium-particle-induced osteolysis without affecting osteoblast function. More importantly, we demonstrated that DHA inhibited breast tumor-induced osteolysis through inhibiting the proliferation, migration and invasion of MDA-MB-231 cells via modulating AKT signaling pathway. In conclusion, DHA effectively inhibited osteoclastogenesis and prevented breast cancer-induced osteolysis.
authors.affiliation: Orthopaedic Department, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, China.
authors.forename: Ming-Xuan
authors.initials: MX
authors.lastname: Feng
authors.affiliation: Orthopaedic Department, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Hong
authors.affiliation: Orthopaedic Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Orthopaedic Department, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, China.
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Fan
authors.affiliation: Orthopaedic Department, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, China.
authors.forename: Chi-Ting
authors.initials: CT
authors.lastname: Yuan
authors.affiliation: Orthopaedic Department, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, China.
authors.forename: Xin-Huan
authors.initials: XH
authors.lastname: Lei
authors.affiliation: Orthopaedic Department, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Orthopaedic Department, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011,China.
authors.forename: An
authors.initials: A
authors.lastname: Qin
authors.affiliation: Orthopaedic Department, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, China.
authors.forename: Hai-Xiao
authors.initials: HX
authors.lastname: Chen
authors.affiliation: Orthopaedic Department, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, China.
authors.forename: Dun
authors.initials: D
authors.lastname: Hong
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects*; D010014:Osteolysis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014025:Titanium / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D037621:Artemisinins; C039060:artenimol; D014025:Titanium; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt