Selaginella tamariscina (Beauv.) possesses antimetastatic effects on human osteosarcoma cells by decreasing MMP-2 and MMP-9 secretions via p38 and Akt signaling pathways.

Abstract

Selaginella tamariscina is a traditional medicinal plant for treatment of some advanced cancers in the Orient. However, the effect of S. tamariscina on metastasis of osteosarcoma and the underlying mechanism remain unclear. We tested the hypothesis that S. tamariscina suppresses cellular motility, invasion and migration and also investigated its signaling pathways. This study demonstrates that S. tamariscina, at a range of concentrations (from 0 to 50 μg/mL), concentration-dependently inhibited the migration/invasion capacities of three osteosarcoma cell lines without cytotoxic effects. Zymographic and western blot analyses revealed that S. tamariscina inhibited the matrix metalloproteinase (MMP)-2 and MMP-9 enzyme activity, as well as protein expression. Western blot analysis also showed that S. tamariscina inhibits phosphorylation of p38 and Akt. Furthermore, SB203580 (p38 inhibitor) and LY294002 (PI3K inhibitor) showed the similar effects as S. tamariscina in U2OS cells. In conclusion, S. tamariscina possesses an antimetastatic activity in osteosarcoma cells by down-regulating MMP-2 and MMP-9 secretions and increasing TIMP-1 and TIMP-2 expressions through p38 and Akt-dependent pathways. S. tamariscina may be a powerful candidate to develop a preventive agent for osteosarcoma metastasis.

• Authors: Jia-Sin Yang, Chiao-Wen Lin, Yih-Shou Hsieh, Hsin-Lin Cheng, Ko-Huang Lue, Shun-Fa Yang, Ko-Hsiu Lu
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 59 Pg. 801-7 (Sep 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 23811101 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Matrix Metalloproteinase Inhibitors
• Neoplasm Proteins
• Plant Extracts
• TIMP1 protein, human
• TIMP2 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• Tissue Inhibitor of Metalloproteinase-2
• Proto-Oncogene Proteins c-akt
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Angiogenesis Inhibitors (isolation & purification, pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Ethnopharmacology
• Humans
• MAP Kinase Signaling System (drug effects)
• Matrix Metalloproteinase 2 (chemistry, metabolism)
• Matrix Metalloproteinase 9 (chemistry, metabolism)
• Matrix Metalloproteinase Inhibitors (isolation & purification, pharmacology)
• Medicine, East Asian Traditional
• Neoplasm Proteins (agonists, antagonists & inhibitors, metabolism)
• Osteosarcoma (drug therapy, metabolism)
• Phosphorylation (drug effects)
• Plant Extracts (isolation & purification, pharmacology)
• Protein Processing, Post-Translational (drug effects)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Selaginellaceae (chemistry)
• Taiwan
• Tissue Inhibitor of Metalloproteinase-1 (agonists, metabolism)
• Tissue Inhibitor of Metalloproteinase-2 (agonists, metabolism)