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Artemisinin inhibits angiogenesis by regulating p38 MAPK/CREB/TSP‐1 signaling pathway in osteosarcoma
Author(s) -
Li Zhi,
Ding Xiaomin,
Wu Haihui,
Liu Chao
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28424
Subject(s) - angiogenesis , mapk/erk pathway , osteosarcoma , creb , cancer research , artemisinin , p38 mitogen activated protein kinases , signal transduction , phosphorylation , microbiology and biotechnology , biology , immunology , transcription factor , plasmodium falciparum , biochemistry , malaria , gene
Osteosarcoma is the most common bone tumor and characterizes a high metastatic potential. In osteosarcoma, angiogenesis is reported to be closely associated with tumor metastasis. Understanding the underlying mechanisms and accordingly developing therapeutic strategies are urgently desired. Antimalarial agent, artemisinin, has been reported to inhibit tumor angiogenesis. However, we still knew little about the effects of artemisinin on angiogenesis and its potential molecular mechanisms in human osteosarcoma. In this study, we found that artemisinin could induce both the expression and secretion of thrombospondin‐1 (TSP‐1) in a dose‐dependent way in osteosarcoma cells. In addition, TSP‐1 could effectively restore the artemisinin‐induced suppression of angiogenesis in human umbilical vein endothelial cells (HUVECs). More importantly, we further found that phosphorylation of cAMP response element‐binding protein (CREB) bond specifically to the promoter of TSP‐1 and promoted its transcriptional activation. Moreover, our results showed that artemisinin could induce the phosphorylation of CREB via the activation of p38 mitogen‐activated protein kinase (MAPK) signaling pathway in osteosarcoma cells. In vivo, we also found that artemisinin could inhibit osteosarcoma proliferation and angiogenesis by regulating the p38 MAPK/CREB/TSP‐1 signaling pathway. Taken together, our findings indicated that artemisinin could inhibit angiogenesis by regulating the p38 MAPK/CREB/TSP‐1 signaling pathway in osteosarcoma.