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KMID : 1200820050050040283
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Oriental Pharmacy and Experimental Medicine
2005 Volume.5 No. 4 p.283 ~ p.293
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DMNQ S-52, a new shikonin derivative, inhibits lymph node metastasis via inhibition of MMPs production
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Lee Soo-Jin
Kim Sung-Hoon
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Abstract
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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 the present study, we investigated its anti-metastatic activities as compared with shikonin because DMNQ S-52 was synthesized for overcoming weak points of shikonin such as high toxicity, low solubility and deleterious effects. DMNQ S-52 showed the weaker cytotoxicity against Lewis lung carcinoma (LLC) cells than that of shikonin . DMNQ S-52, at non-toxic concentrations , significantly inhibited the invasion and migration of LLC cells. DMNQ S-52 also significantly inhibited the production of MMP-9, MTl-MMP and uPAR. Moreover, daily i.p. administration of DMNQ S-52 at dose of 5 mg/kg in mice resulted in a potent inhibition of the primary tumor size of LLC in the lung as well as the metastasis of lymph nodes. These findings suggest that the DMNQ S-52 has therapeutic potential to inhibit metastasis via inhibition of MMP family and uPA/plasminogen system.
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KEYWORD
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DMNQ S-52, Lymph node metastasis, Lewis lung carcinoma, MMP, uPA
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