Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation
- Authors
- Chae, Jung-Il; Cho, Jin Hyoung; Kim, Dong Joon; Lee, Kyung-Ae; Cho, Moon-Kyun; Nam, Hae-Seon; Woo, Kee-Min; Lee, Sang-Han; Shim, Jung-Hyun
- Issue Date
- Jul-2012
- Publisher
- Demetrios A. Spandidos Ed. & Pub.
- Keywords
- juglone; cell transformation; phosphoinositol 3-kinase; anti-protein kinase B; 12-O-tetradecanoylphorbol-13-acetate
- Citation
- International Journal of Molecular Medicine, v.30, no.1, pp 8 - 14
- Pages
- 7
- Journal Title
- International Journal of Molecular Medicine
- Volume
- 30
- Number
- 1
- Start Page
- 8
- End Page
- 14
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/15043
- DOI
- 10.3892/ijmm.2012.969
- ISSN
- 1107-3756
1791-244X
- Abstract
- Juglone (5-hydroxy-1,4-naphthalenedione) from black walnut trees induces apoptosis and inhibits proliferation of various malignant cells. Here, we investigated whether juglone affects 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation through the phosphoinositol 3-kinase (PI3K) pathway. The results showed that TPA- and endothelial growth factor (EGF)-induced anchorage-independent colony formation were suppressed in a dose-dependent manner by treatment of JB6 CI41 mouse skin epidermal cells with juglone (2.5 and 5 mu M). We demonstrated that juglone suppressed PI3K activity via direct binding to PI3K by sepharose 4B pull-down assay and western blot analysis. Juglone significantly suppressed TPA-induced protein kinase B (AKT) and c-Jun phosphorylation and c-fos activation, but not mitogen-activated protein-kinase kinase (MEK), extracellular signaling-regulated kinase (ERK) or 90 kDa ribosomal protein S6 kinasc (RSK) phosphorylation. Juglone significantly blocked activator protein-1 (AP-1) and cyclooxygenase-2 (COX-2) activation more than the PI3K inhibitors LY294002 and wortmannin. Overall, these results showed the anticancer efficacy of juglone targeting PI3K to prevent TPA-induced tumorigenesis.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Biochemistry > 1. Journal Articles
- College of Medicine > Department of Clinical Parasitology > 1. Journal Articles
- College of Medicine > Department of Dermatology > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/15043)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.