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rLj-RGD3 induces apoptosis via the mitochondrial-dependent pathway and inhibits adhesion, migration and invasion of human HeyA8 cells via FAK pathway.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2017 Mar; Vol. 96, pp. 652-668. Date of Electronic Publication: 2016 Dec 27. - Publication Year :
- 2017
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Abstract
- Ovarian carcinoma is a tumor derived from ovary, which brings relatively higher mortality rate among the fatal gynecological cancers. Recently, lots of studies have concentrated on the anti-tumor effects of Arg-Gly-Asp (RGD) motif containing peptides due to their integrin binding properties. In order to meet the criterion of genetic engineering drugs, a recombinant RGD toxin protein (rLj-RGD3) without a His-tag was cloned from the buccal glands of Lampetra japonica in the present study. After endotoxin removal, the His-tag removed rLj-RGD3 was shown to inhibit the proliferation of HeyA8 cells. According to the confocal microscope, flow cytometry and western blot analysis, rLj-RGD3 could trigger HeyA8 cells apoptosis by changing mitochondrial membrane potential, arrangement of F-actin, protein level of BCL2, BAX, caspase 3, and cleaved caspase 3, concentration of cytoplasmic calcium, as well as phosphorylation level of ERK/JNK/p38. Furthermore, rLj-RGD3 was also able to suppress the adhesion, migration, and invasion processes of HeyA8 cells by disturbing the organization of F-actin and reducing the level of p-FAK. In addition, rLj-RGD3 could inhibit the adhesion of HeyA8 cells to extracellular matrix proteins by competitively binding to integrins, indicated that rLj-RGD3 might act as an anti-tumor drug to treat ovarian carcinoma patients in the future.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Antineoplastic Agents pharmacology
Cell Proliferation drug effects
Cell Survival drug effects
Extracellular Signal-Regulated MAP Kinases metabolism
Female
Humans
JNK Mitogen-Activated Protein Kinases metabolism
Neoplasm Invasiveness
Ovarian Neoplasms pathology
Phosphorylation drug effects
Recombinant Proteins pharmacology
Apoptosis drug effects
Cell Adhesion drug effects
Cell Movement drug effects
Focal Adhesion Kinase 1 metabolism
MAP Kinase Signaling System drug effects
Mitochondria drug effects
Oligopeptides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 96
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 28038913
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2016.12.069