title: KU004 induces G1 cell cycle arrest in human breast cancer SKBR-3 cells by modulating PI3K/Akt pathway.
abstract: KU004 is a newly synthesized compound which has been demonstrated possessing potent anti-cancer activities through targeting the highly-expressed protein HER2 on the surface of the cells. In this study, we investigated the potential roles of KU004 in the induced-cell cycle arrest in human breast cancer SK-BR-3 cells. KU004 could not only inhibit the proliferation of SK-BR-3 in a concentration-dependent manner but also induce G1 phase arrest in SK-BR-3 cells. The western blot results showed KU004 decreased the expression of cyclin D, CDK-4, p-Rb708/780, and up-regulated the p21. In order to verify whether KU004 takes the anti-tumor effect thought the regulation of PI3K/Akt pathway, we used western blot to detect the expression of protein Akt, Her2, p-Akt and p-Her2. Our results shown that after KU004 treatment, the amount of p-Akt and p-Her2 decreased but the total amount of Akt and Her2 remained unchanged. In conclusion, these results provide a framework for further exploration of KU004 as a novel chemotherapeutic for human breast tumors by modulating PI3K/Akt pathway.
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 210009 Nanjing, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 210009 Nanjing, PR China.
authors.forename: Chongchong
authors.initials: C
authors.lastname: Tian
authors.affiliation: Department of pathology, University of Illinois at Chicago, 909 S. Wolcott street, 60612 IL, Chicago, USA.
authors.forename: Mengtao
authors.initials: M
authors.lastname: Xing
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 210009 Nanjing, PR China.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 210009 Nanjing, PR China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Guo
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 210009 Nanjing, PR China; Jiangsu Provincial Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, 210009 Nanjing, PR China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Jiangsu Kanion Pharmaceutical Co., Ltd, 222047 Lianyungang, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 210009 Nanjing, PR China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Ministry of Education, 210009 Nanjing, PR China. Electronic address: jiangcpu@163.com.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, 210009 Nanjing, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 210009 Nanjing, PR China. Electronic address: lyzhang@cpu.edu.cn.
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003498:Cyclic P-Oxides / Q000494:pharmacology*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D003498:Cyclic P-Oxides; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C000623229:KU004 compound
keywords: Cell cycle arrest; KU004; PI3K/Akt