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Small molecule BKM1972 inhibits human prostate cancer growth and overcomes docetaxel resistance in intraosseous models.
- Source :
-
Cancer Letters . Apr2019, Vol. 446, p62-72. 11p. - Publication Year :
- 2019
-
Abstract
- Bone metastasis is a major cause of prostate cancer (PCa) mortality. Although docetaxel chemotherapy initially extends patients' survival, in most cases PCa becomes chemoresistant and eventually progresses without a cure. In this study, we developed a novel small-molecule compound BKM1972, which exhibited potent in vitro cytotoxicity in PCa and other cancer cells regardless of their differences in chemo-responsiveness. Mechanistic studies demonstrated that BKM1972 effectively inhibited the expression of anti-apoptotic protein survivin and membrane-bound efflux pump ATP binding cassette B 1 (ABCB1, p-glycoprotein), presumably via signal transducer and activator of transcription 3 (Stat3). BKM1972 was well tolerated in mice and as a monotherapy, significantly inhibited the intraosseous growth of chemosensitive and chemoresistant PCa cells. These results indicate that BKM1972 is a promising small-molecule lead to treat PCa bone metastasis and overcome docetaxel resistance. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 446
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 134733657
- Full Text :
- https://doi.org/10.1016/j.canlet.2019.01.010