DMNQ S-52, a new shikonin derivative, inhibits lymph node metastasis viainhibition of MMPs production > Volume 05 - 2005

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Oriental Pharmacy and Experimental Medicine
Volume 05 - 2005
Date: 2005

Journal: Pages 283-293

December 2005 | DMNQ S-52, a new shikonin derivative, inhibits lymph node metastasis viainhibition of MMPs production…

Soo Jin Lee1,2 and Sung-Hoon Kim2,*

첨부파일

Summary

​Our previous study showed that a novel synthetic shikonin derivative, 6-(1-hydroxyimino-4-methylpentyl)5,8-dimethyoxy 1,4-naphthoquinone S-52 (DMNQ S-52) induced apoptosis. In thepresent study, we investigated its anti-metastatic activities as compared with shikonin becauseDMNQ S-52 was synthesized for overcoming weak points of shikonin such as high toxicity, lowsolubility and deleterious effects. DMNQ S-52 showed the weaker cytotoxicity (IC50; 12.3±1.6 µM)against Lewis lung carcinoma (LLC) cells than that of shikonin (IC50; 4.2 ± 1.1 µM). DMNQ S-52, atnon-toxic concentrations (less than 10 µM), significantly inhibited the invasion and migration ofLLC cells. DMNQ S-52 also significantly inhibited the production of MMP-9, MT1-MMP anduPAR. Moreover, daily i.p. administration of DMNQ S-52 at dose of 5 mg/kg in mice resulted in apotent inhibition of the primary tumor size of LLC in the lung as well as the metastasis of lymphnodes. These findings suggest that the DMNQ S-52 has therapeutic potential to inhibit metastasisvia inhibition of MMP family and uPA/plasminogen system.


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