Background: Celastrol is a novel anti-tumor agent. Ways to further enhance this effect of celastrol has attracted much research attention. Methods and Results: Here, we report that celastrol treatment can elevate miR-223 in human breast cancer cell line MCF-7 and prostate cancer PC3. Down-regulating miR-223 could increase the number of viable cells, yet it further reduced viable cells in samples that were treated by celastrol; up-regulation of miR-223 displayed opposite effects. Celastrol's miR-223 induction might be due to NF-kappa B inhibition and transient mTOR activation: these two events occurred prior to miR-223 elevation in celastrol-treated cells. NF-kappa B inhibitor, like celastrol, could induce miR-223; the induction of miR-223 by NF-kappa B inhibitor or celastrol was reduced by the use of mTOR inhibitor. Finally and interestingly, miR-223 also could affect NF-kappa B and mTOR and the effects were different between cells treated or not treated with celastrol, thus providing an explanation for differing effects of miR-223 alteration on cellular viability in the presence of celastrol or not. Conclusions: For the first time, we disclose that celastrol could induce miR-223 in breast and prostate cancer cells, and that inhibiting miR-223 could further reduce the living cells in celastrol-treated cancer cell lines. We thus provide a novel way to increase celastrol's anti-cancer effects.
[1]Ningxia Med Univ, Dept Clin Lab Diagnost, Postgrad Educ Coll, Yinchuan 750004, Peoples R China.
[2]Second Mil Med Univ, Shanghai Gongli Hosp, Sinofrench Cooperat Cent Lab, Shanghai 200135, Peoples R China.
[3]Shanghai Fudan Univ, Zhong Shan Hosp, Dept Pharmaceut, Shanghai 200032, Peoples R China.
[4]Hop Paul Brousse, INSERM, U972, F-94807 Villejuif, France.
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