title: YSY01A, a Novel Proteasome Inhibitor, Induces Cell Cycle Arrest on G2 Phase in MCF-7 Cells via ERα and PI3K/Akt Pathways.
abstract: Given that the proteasome is essential for multiple cellular processes by degrading diverse regulatory proteins, inhibition of the proteasome has emerged as an attractive target for anti-cancer therapy. YSY01A is a novel small molecule compound targeting the proteasome. The compound was found to suppress viability of MCF-7 cells and cause limited cell membrane damage as determined by sulforhodamine B assay (SRB) and CytoTox 96(®) non-radioactive cytotoxicity assay. High-content screening (HCS) further shows that YSY01A treatment induces cell cycle arrest on G2 phase within 24 hrs. Label-free quantitative proteomics (LFQP), which allows extensive comparison of cellular responses following YSY01A treatment, suggests that various regulatory proteins including cell cycle associated proteins and PI3K/Akt pathway may be affected. Furthermore, YSY01A increases p-CDC-2, p-FOXO3a, p53, p21(Cip1) and p27(Kip1) but decreases p-Akt, p-ERα as confirmed by Western blotting. Therefore, YSY01A represents a potential therapeutic for breast cancer MCF-7 by inducing G2 phase arrest via ERα and PI3K/Akt pathways.
authors.affiliation: 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, China;
authors.forename: Bingjie
authors.initials: B
authors.lastname: Xue
authors.affiliation: 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, China;
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, China;
authors.forename: Xia
authors.initials: X
authors.lastname: Yuan
authors.affiliation: 2. Instrumental Analysis Center of State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, China;
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: 3. Lab of Proteomics Medical and Healthy Analytical Center, Peking University, Beijing, China;
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Lou
authors.affiliation: 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, China;
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, China;
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Ran
authors.affiliation: 4. Peking University School of Pharmaceutical Sciences Department of Medicinal Chemistry, Beijing, China.
authors.forename: Zemei
authors.initials: Z
authors.lastname: Ge
authors.affiliation: 4. Peking University School of Pharmaceutical Sciences Department of Medicinal Chemistry, Beijing, China.
authors.forename: Runtao
authors.initials: R
authors.lastname: Li
authors.affiliation: 1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, China;
authors.forename: Jingrong
authors.initials: J
authors.lastname: Cui
keywords: ERα; High-content screening; Label-free quantitative proteomics; MCF-7; PI3K/Akt pathways; PS341; YSY01A