Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel-7402 cells

•rhddADAM15 inhibited the proliferation and migration of Bel-7402 cells.•rhddADAM15 inhibited growth and metastasis of Bel-7402 cells in zebrafish xenograft.•rhddADAM15 induced apoptosis in Bel-7402 cells and somatic cells of zebrafish.•Cell-cycle in Bel-7402 cells showed a partial G2/S arrest.•Acti...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2013-06, Vol.435 (4), p.640-645
Main Authors: Hou, Y., Chu, M., Du, F.F., Lei, J.Y., Chen, Y., Zhu, R.Y., Gong, X.H., Ma, X., Jin, J.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
ADAM Proteins - genetics
ADAM Proteins - pharmacology
ADAM15
APOPTOSIS
Bel-7402 cells
Cell Line, Tumor
Cell Movement - drug effects
Cell Proliferation - drug effects
Danio rerio
Disintegrin
Disintegrins - genetics
Disintegrins - pharmacology
Humans
IN VITRO
IN VIVO
Liver Neoplasms - pathology
Liver Neoplasms - physiopathology
Membrane Proteins - genetics
Membrane Proteins - pharmacology
METASTASES
Migration
NEOPLASMS
Proliferation
Protein Structure, Tertiary
Recombinant Proteins - pharmacology
SOMATIC CELLS
Zebrafish
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Summary:•rhddADAM15 inhibited the proliferation and migration of Bel-7402 cells.•rhddADAM15 inhibited growth and metastasis of Bel-7402 cells in zebrafish xenograft.•rhddADAM15 induced apoptosis in Bel-7402 cells and somatic cells of zebrafish.•Cell-cycle in Bel-7402 cells showed a partial G2/S arrest.•Activity of caspases 8, 9 and 3 was increased in rhddADAM15-treated Bel-7402 cells. ADAM15 (A Disintegrin And Metalloproteinase 15), a transmembrane protein containing seven domains, interacts with some integrins via its disintegrin domain and overexpresses in many solid tumors. In this study, the effect of the recombinant human disintegrin domain (rhddADAM15) on the proliferation and migration of Bel-7402 cells was evaluated in vitro and in vivo in zebrafish xenografts. rhddADAM15 (4μM) severely inhibited the proliferation and migration of Bel-7402 cells, inducing a partial G2/S arrest and morphological nucleus changes of apoptosis. Moreover, the activity of caspases 8, 9 and 3 in Bel-7402 cells was increased. In addition, the zebrafish was used as a model for apoptosis-induction and tumor-xenograft. rhddADAM15 (1pM) inhibited the growth and metastasis of Bel-7402 cell xenografts in zebrafish and a lower concentration (0.1pM) induced severe apoptosis in the somatic cells of zebrafish. In conclusion, our data identified rhddADAM15 as a potent inhibitor of tumor growth and metastasis, making it a promising tool for use in anticancer treatment.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2013.05.037