A new proteasome inhibitor YSY-01A induced autophagy in PC-3M cells

doi:10.5246/jcps.2014.08.073

Journal of Chinese Pharmaceutical Sciences

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A new proteasome inhibitor YSY-01A induced autophagy in PC-3M cells

Zhe Wang¹, Xia Yuan¹, Zemei Ge², Fuxiang Ran¹, Jun Wu¹, Runtao Li^2*, Jingrong Cui^1*

1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China
2. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2014-05-04 Revised:2014-05-14 Online:2014-08-31 Published:2014-06-01
Contact: Tel.: 86-10-82802467, 86-10-82801504
Supported by:
Eleventh FiveYear Plan for National Science and Technology Major Project (Grant No. 2009ZX0930010), National Science Foundation of China (Grant No. 81172915) and a grant from Major New Drugs Research and Development Platform of Peking University (Grant No. 2009ZX09301010).

Abstract

Abstract:

YSY-01A has shown proliferation inhibitory activity to certain types of tumor cells by inhibiting proteasome. However, its effect on autophagy, which is related with the ubiquitin proteasome pathway (UPP), remains unclear. Our study aimed to find out its effect on autophagy and possible molecular mechanisms. The results suggested that YSY-01A significantly (P<0.001) inhibited proliferation of PC-3M cells (IC₅₀ was 287 nM for 48 h) in a concentration-dependent and time-dependent manner. YSY-01A (100 nM, 3 h) also induced autophagy in PC-3M cells through increasing the expression of P53 (P<0.001), Beclin-1 (P<0.001) and LC3 (P<0.001), and decreasingthe expression of p-mTOR (P<0.001) as compared with the negative control group. Autophagy stayed at a final stage in PC-3M cells after treated with YSY-01A(400 nM)for 12 h. Meanwhile inhibition of autophagy with chloroquine increased the sensitivity to YSY-01A in PC-3M cells. In conclusion, YSY-01A showed high proliferation inhibitory activity of PC-3M cells and it could induce autophagy in PC-3M cells. Inhibiting autophagy increased the cytotoxic activity of YSY-01A in PC-3M cells.

Key words: Proteasome inhibitor, YSY-01A, PC-3M, Autophagy

CLC Number:

R962

Supporting:

Zhe Wang, Xia Yuan, Zemei Ge, Fuxiang Ran, Jun Wu, Runtao Li, Jingrong Cui. A new proteasome inhibitor YSY-01A induced autophagy in PC-3M cells[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2014.08.073.

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A new proteasome inhibitor YSY-01A induced autophagy in PC-3M cells

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