Selaginella tamariscina (Beauv.) possesses antimetastatic effects on human osteosarcoma cells by decreasing MMP-2 and MMP-9 secretions via p38 and Akt signaling pathways |
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| Affiliation: | 1. Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan;2. Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan;3. Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan;4. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan;5. School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan;6. Department of Medical Research, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan;7. Department of Orthopedics, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan;1. Department of Pharmacology, Medical College, Yangzhou University, Yangzhou 225001, Jiangsu, China;2. Department of Combination of traditional Chinese and Western Medicine, Medical College, Yangzhou University, Yangzhou 225001, Jiangsu, China;3. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu, China;1. Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China;2. Jiangsu Provincial Key Laboratory for Plant Ex Situ Conservation, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China;1. Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan;2. School of Medicine, Chung Shan Medical University, No. 110, Section 1, Jiankuo North Road, Taichung 40201, Taiwan;3. Department of Surgery, Division of Colon and Rectum, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung 40201, Taiwan;4. Department of Medical Research, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung 40201, Taiwan |
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| 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. |
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| Keywords: | Metastasis Osteosarcoma MMP-2 MMP-9 ECM" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" extracellular matrix ERK" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" extracellular signal-regulated protein kinase JNK" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" c-Jun N-terminal kinase MAPK" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" mitogen-activated protein kinase MMP" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" matrix metalloproteinase PI3K" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" phosphatidylinositol 3-kinase TIMP" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" tissue inhibitor of metalloproteinase |
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