Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. METHODS: To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected), D341 (c-MYC amplification) and D425 (c-MYC amplification) human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. RESULTS: NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml) and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. CONCLUSION: In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit proliferation of human MB cells in vivo

マツ材線虫病誘導抵抗性の物質的解明

研究期間:平成14-16年度 ; 研究種目:基盤研究C2 ; 課題番号:14560120原著には既発表論文の別刷を含む

Gas liquid chromatographic determination of canthinone alkaloids inHannoa chlorantha root bark and tissue cultures

A capillary gas chromatographic method has been developed for the determination of canthinone alkaloids. The method was applied to the semi-quantitative determination of canthin-6-one, 1-methoxycanthin-6-one, 1-hydroxycanthin-6-one, 8-hydroxycanthin-6-one, 10-hydroxycanthin-6-one, and canthin-6-one-3-N-oxide in callus and shoot cultures, and in root barks of Hannoa chlorantha. The results showed that their concentrations were highly dependent on the sample origin and on the culture conditions.SCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe