title: The iron chelator Dp44mT suppresses osteosarcoma's proliferation, invasion and migration: in vitro and in vivo.
abstract: Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), the novel iron chelator, has been reported to inhibit the tumorigenesis and progression of various cancer cells, including neuroblastoma, neuroepithelioma and prostate cancer. However, whether Dp44mT has anticancer effects in osteosarcoma is still unknown. Here, we investigated the antitumor action of Dp44mT in osteosarcoma and its underlying mechanisms. A human osteosarcoma 143B cell linein vitroand 143B xenograft in nude micein vivowere utilized, the anticancer effects of Dp44mT were examined through methods of MTT assay, transwell, wound healing assay, flow cytometry, western blot, immunohistochemistry and H&E staining. We showed that Dp44mT inhibits cell proliferation, invasion and migrationin vitro. In addition, flow cytometry further illustrated that Dp44mT suppression of 143B cell proliferation, invasion and migration were partially due to induction of cell apoptosis, cell cycle arrest in S phase and ROS production. Alsoin vitroandin vivo, the expression levels of Bcl2, Bax, Caspase3, Caspase9, LC3-II, β-catenin and its downstream targets such as C-myc and Cyclin D1 demonstrated that cell apoptosis and autophagy, as well as Wnt/β-catenin pathway were involved in Dp44mT induced osteosarcoma suppression. The Dp44mT inhibition of osteosarcoma was further verified via animal models. The findings indicated thatin vivoDp44mT showed a significant reduction in the 143B xenograft tumor growth and metastasis. In conclusion, our data demonstrated that Dp44mT has effective anticancer capability in osteosarcoma and that may represent a promising treatment strategy for osteosarcoma.
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan UniversityWuhan 430071, Hubei, China; Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford UniversityStanford, CA, USA.
authors.forename: Kangquan
authors.initials: K
authors.lastname: Shou
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan UniversityWuhan 430071, Hubei, China; Department of Biochemistry & Molecular Medicine, UC Davis School of MedicineSacramento 95871, CA, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Jian
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei, China.
authors.forename: Wanrong
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, Zhongnan Hospital of Wuhan University Wuhan 430071, Hubei, China.
authors.forename: Aixi
authors.initials: A
authors.lastname: Yu
keywords: Dp44mT; invasion; migration; osteosarcoma; proliferation