Oligomannurarate sulfate inhibits CXCL12/SDF-1-mediated proliferation and invasion of human tumor cells in vitro.

Abstract

AIM:

JG6 is a novel marine-derived oligosaccharide that has shown to inhibit angiogenesis and tumor metastasis. In this study, we sought to identify the potential target responsible for the anti-cancer activity of JG6.

METHODS:

Human liver cancer cell line Bel-7402 and human cervical cancer cell line HeLa were examined. CXCL12-stimulated cell proliferation and migration were determined using a CCK-8 kit and a transwell assay, respectively. Western blotting was performed to examine the changes in CXCL12/CXCR4 axis. Molecular docking and surface plasmon resonance (SPR) were performed to characterize the possible interaction between JG6 and the CXCL12/CXCR4 axis.

RESULTS:

Treatment with CXCL12 potently stimulated the proliferation and migration in both Bel-7402 and HeLa cells. Co-treatment of the cells with JG6 (10, 50 and 100 μg/mL) dose-dependently impeded the CXCL12-stimulated cell proliferation and migration. Furthermore, CXCL12 rapidly induced phosphorylation of AKT, ERK, FAK and Paxillin in Bel-7402 and HeLa cells, whereas pretreatment with JG6 dose-dependently inhibited the CXCL12-induced phosphorylation of these proteins. The SPR assay showed that JG6 bound to CXCL12 with a high affinity. In molecular docking study, JG6 appeared to interact with CXCL12 via multiple polar interactions, including 6 ionic bonds and 7 hydrogen bonds.

CONCLUSION:

Inhibition of the CXCL12/CXCR4 axis by JG6 may account for its anticancer activity.

• Authors: Wei-wei Wen, Shao Xie, Xian-liang Xin, Mei-yu Geng, Jian Ding, Yi Chen
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 34 Issue 12 Pg. 1554-9 (Dec 2013) ISSN: 1745-7254 [Electronic] United States
• PMID: 24141568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CXCL12 protein, human
• Chemokine CXCL12
• Mannans
• Neoplasm Proteins
• oligomannurarate sulfate

Topics

• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chemokine CXCL12 (antagonists & inhibitors, physiology)
• Dose-Response Relationship, Drug
• Female
• Humans
• Liver Neoplasms (metabolism, pathology)
• Mannans (pharmacology)
• Neoplasm Invasiveness (prevention & control)
• Neoplasm Proteins (metabolism)
• Phosphorylation
• Surface Plasmon Resonance
• Uterine Cervical Neoplasms (metabolism, pathology)