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- Title
Total Synthetic Protoapigenone WYC02 Inhibits Cervical Cancer Cell Proliferation and Tumour Growth through PIK3 Signalling Pathway.
- Authors
Chen, Yun‐Ju; Kay, Nari; Yang, Jinn‐Moon; Lin, Chih‐Ta; Chang, Hsueh‐Ling; Wu, Yang‐Chang; Fu, Chi‐Feng; Chang, Yu; Lo, Steven; Hou, Ming‐Feng; Lee, Yi‐Chen; Hsieh, Ya‐Ching; Yuan, Shyng‐Shiou
- Abstract
Flavonoids have been intensively explored for their anticancer activity. In this study, a total synthetic flavonoid protoapigenone, known as WYC02, was analysed for its potential anticancer activity on human cervical cancer cells as well as the underlying mechanisms for these effects. The site-moiety maps are used to explore the binding site similarity, pharmacophore and docking pose similarity. The effect of WYC02 on cell viability, migration, invasion and apoptosis as well as the underlying mechanisms was analysed in vitro using human cervical cancer cells. The effect of WYC02 on in vivo tumour growth was assessed in a tumour xenograft study. WYC02 inhibited cell proliferation, MMPs activity, migration and invasion in cervical cancer cells. We speculated that WYC02 might inhibit the activities of PIK3 family proteins, including PIK3 CA, PIK3 CB, PIK3 CD and PIK3 CG. Indeed, WYC02 decreased the expression of PIK3 family proteins, especially PIK3 CG, through ubiquitination and inhibited the activities of PIK3 CG and PIK3 downstream molecules AKT1 and MTOR in cervical cancer cells. Furthermore, PIK3 signalling pathway was involved in the inhibitory effect of WYC02 on cervical cancer cell proliferation and tumour growth in vitro and in vivo. WYC02 inhibits cervical cancer cell proliferation and tumourigenesis via PIK3 signalling pathway and has the potential to be developed as a chemotherapeutic agent in cervical cancer.
- Subjects
CERVICAL cancer diagnosis; CANCER cell proliferation; CANCER invasiveness; FLAVONOIDS; ANTINEOPLASTIC agents; PHOSPHATIDYLINOSITOL 3-kinases; SIGNALING (Psychology); THERAPEUTICS
- Publication
Basic & Clinical Pharmacology & Toxicology, 2013, Vol 113, Issue 1, p8
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/bcpt.12057