J Cancer 2015; 6(4):319-326. doi:10.7150/jca.10733 This issue Cite
1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, China;
2. Instrumental Analysis Center of State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 100083, Beijing, China;
3. Lab of Proteomics Medical and Healthy Analytical Center, Peking University, Beijing, China;
4. Peking University School of Pharmaceutical Sciences Department of Medicinal Chemistry, Beijing, China
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, p21Cip1 and p27Kip1 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.
Keywords: YSY01A, PS341, MCF-7, High-content screening, Label-free quantitative proteomics, ERα, PI3K/Akt pathways