A Novel Derivative of the Natural Agent Deguelin for Cancer Chemoprevention and Therapy
- Authors
- Kim, WY; Chang, DJ; Hennessy, B; Kang, HJ; Yoo, J; Han, SH; Kim, YS; Park, HJ; Geo, SY; Mills, G; Kim, KW; Hong, WK; Suh, YG; Lee, HY
- Issue Date
- Dec-2008
- Publisher
- aacr
- Citation
- CANCER PREVENTION RESEARCH, v.1, no.7, pp 577 - 587
- Pages
- 11
- Journal Title
- CANCER PREVENTION RESEARCH
- Volume
- 1
- Number
- 7
- Start Page
- 577
- End Page
- 587
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/148143
- DOI
- 10.1158/1940-6207.CAPR-08-0184
- ISSN
- 1940-6207
1940-6215
- Abstract
- The natural compound deguelin has promising preventive and therapeutic activity against diverse cancers by directly binding to heat shock protein-90 and thus suppressing its function. Potential side effects of deguelin over a certain dose, however, could be a substantial obstacle to its clinical use. To develop a derivative(s) of deguelin with reduced potential side effects, we synthesized five deguelin analogues (SH-02, SH-03, SH-09, SH-14, and SH-15) and compared them with the parent compound and each other for structural and biochemical features; solubility; and antiproliferative effects on normal, premalignant, and malignant human bronchial epithelial (HBE) and non-small-cell lung cancer (NSCLC) cell lines. Four derivatives destabilized hypoxia-inducible factor-1 alpha as potently as did deguelin. Reverse-phase protein array (RPPA) analysis in H460 NSCLC cells revealed that deguelin and the derivatives suppressed expression of a number of proteins including heat shock protein-90 clients and proteins involved in the phosphoinositide 3-kinase/Akt pathway. One derivative, SH-14, showed several features of potential superiority for clinical use: the highest apoptotic activity; no detectable influence on Src/signal transducer and activator of transcription signaling, which can promote cancer progression and is cl
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