4-Methoxydalbergione suppresses growth and induces apoptosis in human osteosarcoma cells in vitro and in vivo xenograft model through down-regulation of the JAK2/STAT3 pathway
| Autor: | Q-Schick Auh, Hyuncheol Oh, Hyung-Mun Yun, Dong-Sung Lee, Tran-Hong Quang, Eun-Cheol Kim, Kyung-Ran Park |
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| Rok vydání: | 2016 |
| Předmět: |
Male
STAT3 Transcription Factor 0301 basic medicine MAPK/ERK pathway Blotting Western Mice Nude Dalbergia odorifera Apoptosis Bone Neoplasms 4-methoxydalbergione Immunoenzyme Techniques Mice 03 medical and health sciences Downregulation and upregulation In vivo Annexin osteosarcoma Survivin Benzoquinones Tumor Cells Cultured Animals Humans Medicine Phosphorylation STAT3 Cell Proliferation Mice Inbred BALB C biology business.industry JAK2/STAT3 Janus Kinase 2 medicine.disease Xenograft Model Antitumor Assays MAPK Gene Expression Regulation Neoplastic 030104 developmental biology Oncology Immunology Cancer research biology.protein Osteosarcoma business Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Although the heartwood of Dalbergia odorifera T. Chen (Leguminosae) is an important source of traditional Korean and Chinese medicines, the effects of novel compound methoxydalbergione (4-MD) isolated from Dalbergia odorifera was not reported. Herein, we investigated the effects of the 4-MD in vitro and in vivo against osteosarcoma cells and its molecular mechanisms. 4-MD inhibited the proliferation of osteosarcoma cells and induced apoptosis as evidenced by Annexin V + and TUNEL + cells. This apoptosis was accompanied by upregulation of apoptotic proteins (procaspase-3 and PARP), but downregulation of anti-apoptotic proteins (Bcl-2, Bcl-xL, and Survivin). 4-MD inhibited phosphorylation of JAK2 and STAT3 with the inactivation of mitogen-activated protein kinases (MAPKs) and CREB, and the upregulation of PTEN in osteosarcoma cells. Importantly, 4-MD reduced colony formation in soft agar and inhibited tumor growth in mice xenograft model in association with the reduced expression of PCNA, Ki67, p-STAT3, and Survivin. Taken together, the present study for the first time demonstrates that 4-MD exerts in vitro and in vivo anti-proliferative effects against osteosarcoma cells through the inhibition of the JAK2/STAT3 pathway, and suggest the potential for therapeutic application of 4-MD in the treatment of osteosarcoma. |
| Databáze: | OpenAIRE |
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