title: Total synthetic protoapigenone WYC02 inhibits cervical cancer cell proliferation and tumour growth through PIK3 signalling pathway.
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 PIK3CA, PIK3CB, PIK3CD and PIK3CG. Indeed, WYC02 decreased the expression of PIK3 family proteins, especially PIK3CG, through ubiquitination and inhibited the activities of PIK3CG 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.
authors: Department of Biological Science and Technology, I-Shou University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, E-DA Hospital, Kaohsiung, Taiwan.
authors: Yun-Ju
authors: YJ
authors: Chen
authors: Nari
authors: N
authors: Kay
authors: Jinn-Moon
authors: JM
authors: Yang
authors: Chih-Ta
authors: CT
authors: Lin
authors: Hsueh-Ling
authors: HL
authors: Chang
authors: Yang-Chang
authors: YC
authors: Wu
authors: Chi-Feng
authors: CF
authors: Fu
authors: Yu
authors: Y
authors: Chang
authors: Steven
authors: S
authors: Lo
authors: Ming-Feng
authors: MF
authors: Hou
authors: Yi-Chen
authors: YC
authors: Lee
authors: Ya-Ching
authors: YC
authors: Hsieh
authors: Shyng-Shiou
authors: SS
authors: Yuan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003512:Cyclohexanones / Q000494:pharmacology*; D005260:Female; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D020539:Sequence Analysis, Protein; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D003512:Cyclohexanones; D047309:Flavones; D005419:Flavonoids; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C524112:protoapigenone; C546842:MTOR protein, human; C494918:AKT1 protein, human