Identification of a phenanthrene derivative as a potent anticancer drug with Pim kinase inhibitory activity
スポンサーリンク
概要
- 論文の詳細を見る
Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in malignant lesions, but not in normal tissues, of endoderm-derived organs, including the pancreas, liver, colon, and stomach. Furthermore, the development of hepatocellular carcinoma is accelerated in mice expressing Pim-3 transgene selectively in the liver when these mice are treated with a hepatocarcinogen. These observations suggest that a chemical targeting Pim-3 kinase may be a novel type of anticancer drug. In the present study, we screened low molecular weight chemicals and observed that the phenanthrene derivative T26 potently inhibited Pim-3 and Pim-1, but only weakly inhibited Pim-2. Moreover, T26 markedly inhibited the in vitro growth of human pancreatic cancer cell lines by inducing apoptosis and G 2/M arrest. The growth inhibitory effects of T26 were reversed by overexpression of Pim-3 cDNA in human pancreatic cancer cells, indicating that T26 acts primarily on Pim-3. Furthermore, T26 inhibited the growth of a human pancreatic cancer cell line in nude mice without causing apparent adverse effects when it was administered after tumor formation was evident. These observations imply that the chemical and its related compounds may be effective for the treatment of cancers in which there is aberrant Pim-3 expression. © 2011 Japanese Cancer Association.
論文 | ランダム
- 細菌のChemotaxonomy
- 螢光抗体法(細胞化学シリーズ-3-)
- EFFICIENT SYNTHESIS OF PAEONILACTONE-A AND -B FROM (-)-CARVONE
- 11.経時的な肛門側への腸瘻移動により排便機能を獲得できたhypoganglionosisの1例(一般演題,第37回日本小児消化管機能研究会)
- P-003A 先天性胆道拡張症に合併する脂肪酸カルシウム石 : 蛋白栓とは異なる閉塞原因について(肝・胆道1, 第44回日本小児外科学会学術集会)