Catalpol suppresses osteosarcoma cell proliferation through blocking epithelial-mesenchymal transition (EMT) and inducing apoptosis

Catalpol, an iridoid glucoside compound, is reported to possess diverse pharmacological actions. However, its effects on osteosarcoma are little to be known. In the present study, we showed that catalpol could strongly suppress osteosarcoma progression. Catalpol dose-dependently reduced the cancer c...

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Veröffentlicht in:Biochemical and biophysical research communications 2018-01, Vol.495 (1), p.27-34
Hauptverfasser: Wang, Lei, Xue, Gui-Bin
Format: Artikel
Sprache:eng
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Zusammenfassung:Catalpol, an iridoid glucoside compound, is reported to possess diverse pharmacological actions. However, its effects on osteosarcoma are little to be known. In the present study, we showed that catalpol could strongly suppress osteosarcoma progression. Catalpol dose-dependently reduced the cancer cell viability. The migration of osteosarcoma cells was also consistently suppressed by catalpol treatment using the wound healing and transwell migration analysis. Catalpol reduced the expressions of Kras, receptor for activated C-kinase 1(RACK1) and matrix metalloproteinase (MMP)-2 in a dose-dependent manner, revealing the blockage of migration. Moreover, both intrinsic and extrinsic apoptosis were triggered by catalpol, as evidenced by improved cleaved Caspase-8/-9/-3 and Poly-(ADP-ribose) polymerase (PARP). Release of Cyto-c in cytoplasm and Bax up-regulation in total cells were observed in catalpol-treated cells, while mitochondrial Cyto-c and cellular Bcl-2 were down-regulated by catalpol. Reactive oxygen species (ROS) production was also involved in catalpol-induced cell death. Further, ROS scavenger, N-acetylcysteine (NAC), impeded catalpol-caused apoptosis. And suppression of signal transducer and activator of transcription 3/Janus kinase 2 gene/Src (STAT3/JAK2/Src) was involved in catalpol-induced cell death. In vivo, catalpol showed effective ability to reduce the tumor growth. Our results illustrated that catalpol might be considered as a promising pharmacological agent to suppress osteosarcoma. •Catalpol inhibits cell viability and EMT in osteosarcoma cell lines.•Catalpol induces apoptosis in osteosarcoma cell lines by Bcl-2/Caspase-8 signaling.•Catalpol induces ROS generation and suppresses STAT3 pathway activation.•Catalpol is able to suppresses osteosarcoma growth in vivo.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2017.10.054