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Total Synthetic Protoapigenone WYC 02 Inhibits Cervical Cancer Cell Proliferation and Tumour Growth through PIK 3 Signalling Pathway
Author(s) -
Chen YunJu,
Kay Nari,
Yang JinnMoon,
Lin ChihTa,
Chang HsuehLing,
Wu YangChang,
Fu ChiFeng,
Chang Yu,
Lo Steven,
Hou MingFeng,
Lee YiChen,
Hsieh YaChing,
Yuan ShyngShiou
Publication year - 2013
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12057
Subject(s) - cell growth , apoptosis , in vivo , cancer research , cervical cancer , pi3k/akt/mtor pathway , in vitro , cell culture , cancer cell , pharmacophore , chemistry , hela , cell , cancer , biology , biochemistry , genetics
Flavonoids have been intensively explored for their anticancer activity. In this study, a total synthetic flavonoid protoapigenone, known as WYC 02, 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 WYC 02 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 WYC 02 on in vivo tumour growth was assessed in a tumour xenograft study. WYC 02 inhibited cell proliferation, MMP s activity, migration and invasion in cervical cancer cells. We speculated that WYC 02 might inhibit the activities of PIK 3 family proteins, including PIK 3 CA , PIK 3 CB , PIK 3 CD and PIK 3 CG . Indeed, WYC 02 decreased the expression of PIK 3 family proteins, especially PIK 3 CG , through ubiquitination and inhibited the activities of PIK 3 CG and PIK 3 downstream molecules AKT 1 and MTOR in cervical cancer cells. Furthermore, PIK 3 signalling pathway was involved in the inhibitory effect of WYC 02 on cervical cancer cell proliferation and tumour growth in vitro and in vivo . WYC 02 inhibits cervical cancer cell proliferation and tumourigenesis via PIK 3 signalling pathway and has the potential to be developed as a chemotherapeutic agent in cervical cancer.