Advances in Traditional Medicine

Kyung Hee Oriental Medicine Research Center (경희대학교 융합한의과학연구소)
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DMNQ S-52, a new shikonin derivative, inhibits lymph node metastasis via inhibition of MMPs production

  • Lee, Soo-Jin (Department of Physiology, College of Oriental Medicine, Sangji University,Department of Oncology, Graduate School of East-West Medical Science, Kyunghee University) ;
  • Kim, Sung-Hoon (Department of Oncology, Graduate School of East-West Medical Science, Kyunghee University)
  • Published : 2005.12.30
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Abstract

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 $(IC_{50};\;12.3{\pm}1.6\;{\mu}M)$ against Lewis lung carcinoma (LLC) cells than that of shikonin $(IC_{50};\;4.2{\pm}1.1\;{\mu}M)$. DMNQ S-52, at non-toxic concentrations $(less\;than\;10\;{\mu}M)$, 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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References

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