J Cancer 2015; 6(4):319-326. doi:10.7150/jca.10733 This issue Cite

Research Paper

YSY01A, a Novel Proteasome Inhibitor, Induces Cell Cycle Arrest on G2 Phase in MCF-7 Cells via ERα and PI3K/Akt Pathways

Bingjie Xue1, Wei Huang1, Xia Yuan1, Bo Xu2, Yaxin Lou3, Quan Zhou1, Fuxiang Ran1, Zemei Ge4, Runtao Li4✉, Jingrong Cui1✉

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

Citation:
Xue B, Huang W, Yuan X, Xu B, Lou Y, Zhou Q, Ran F, Ge Z, Li R, Cui J. YSY01A, a Novel Proteasome Inhibitor, Induces Cell Cycle Arrest on G2 Phase in MCF-7 Cells via ERα and PI3K/Akt Pathways. J Cancer 2015; 6(4):319-326. doi:10.7150/jca.10733. https://www.jcancer.org/v06p0319.htm
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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, 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


Citation styles

APA
Xue, B., Huang, W., Yuan, X., Xu, B., Lou, Y., Zhou, Q., Ran, F., Ge, Z., Li, R., Cui, J. (2015). YSY01A, a Novel Proteasome Inhibitor, Induces Cell Cycle Arrest on G2 Phase in MCF-7 Cells via ERα and PI3K/Akt Pathways. Journal of Cancer, 6(4), 319-326. https://doi.org/10.7150/jca.10733.

ACS
Xue, B.; Huang, W.; Yuan, X.; Xu, B.; Lou, Y.; Zhou, Q.; Ran, F.; Ge, Z.; Li, R.; Cui, J. YSY01A, a Novel Proteasome Inhibitor, Induces Cell Cycle Arrest on G2 Phase in MCF-7 Cells via ERα and PI3K/Akt Pathways. J. Cancer 2015, 6 (4), 319-326. DOI: 10.7150/jca.10733.

NLM
Xue B, Huang W, Yuan X, Xu B, Lou Y, Zhou Q, Ran F, Ge Z, Li R, Cui J. YSY01A, a Novel Proteasome Inhibitor, Induces Cell Cycle Arrest on G2 Phase in MCF-7 Cells via ERα and PI3K/Akt Pathways. J Cancer 2015; 6(4):319-326. doi:10.7150/jca.10733. https://www.jcancer.org/v06p0319.htm

CSE
Xue B, Huang W, Yuan X, Xu B, Lou Y, Zhou Q, Ran F, Ge Z, Li R, Cui J. 2015. YSY01A, a Novel Proteasome Inhibitor, Induces Cell Cycle Arrest on G2 Phase in MCF-7 Cells via ERα and PI3K/Akt Pathways. J Cancer. 6(4):319-326.

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