新的蛋白酶体抑制剂YSY-01A对SK-OV-3细胞的周期阻滞作用

doi:10.5246/jcps.2013.06.070

中国药学(英文版)

新的蛋白酶体抑制剂YSY-01A对SK-OV-3细胞的周期阻滞作用

贾璇, 袁霞, 楚明明, 冉福香, 李润涛^*, 崔景荣^*

1. 北京大学医学部天然药物及仿生药物国家重点实验室, 北京 100191
2. 北京大学医学部药学院化学生物学系, 北京 100191

收稿日期:2013-05-06 修回日期:2013-05-24 出版日期:2013-11-15 发布日期:2014-01-22
通讯作者: 李润涛*, 崔景荣*

Cell cycle arrest effect of compound YSY-01A, a new proteasome inhibitor, on SK-OV-3 cells

Xuan Jia, Xia Yuan, Mingming Chu, Fuxiang Ran, Runtao Li^*, Jingrong Cui^*

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:2013-05-06 Revised:2013-05-24 Online:2013-11-15 Published:2014-01-22
Contact: Runtao Li*, Jingrong Cui*

摘要/Abstract

摘要：

化合物YSY-01A是一种新合成的蛋白酶体抑制剂, 前期研究已经证实其具有良好的抑制肿瘤增殖作用, 但是其作用机制尤其是对细胞周期的阻滞作用仍不清楚。本实验旨在评价YSY-01A的抗肿瘤作用与细胞周期阻滞的关系, 并探讨可能的分子机制。结果表明, YSY-01A能够显著抑制卵巢癌细胞SK-OV-3的增殖 (P<0.05), 且具有浓度和时间依赖性。进一步实验表明, YSY-01A能够引起SK-OV-3细胞G₂/M周期阻滞, 显著上调cyclin B1, cdc2和p-cdc2 (T14) 等蛋白的表达 (P<0.05); YSY-01A亦可抑制由TNF-α引起的NF-κB核转位, 同时上调IκBα、下调IKK和 Gadd45α的表达水平。总之, YSY-01A对SK-OV-3细胞具有显著的增殖抑制作用, 其分子机制与G2/M细胞周期阻滞有关。

关键词: 蛋白酶体抑制剂, YSY-01A, SK-OV-3, 细胞周期相关蛋白, 高内涵筛选

Abstract:

Compound YSY-01A, a recently synthesized proteasome inhibitor, has shown potent growth-inhibitory effect on tumor cells in previous researches. However, the mechanism of its inhibitory effects, especially on cell cycle, remains largely unclear. This study aimed to evaluate the correlation between cell cycle arrest effect of YSY-01A and its anti-cancer effect, and to probe the possible molecular mechanisms for its effects on human ovarian cancer SK-OV-3 cells. The results suggested that YSY-01A significantly (P<0.05) inhibited cellular proliferation of SK-OV-3 cells in a concentration-dependent and time-dependent manner. Furthermore, YSY-01A induced a G2/M cell cycle arrest of SK-OV-3 cells. Further investigation revealed that YSY-01A significantly (P<0.05) changed the expression levels of a series of cell cycle related protein, such as cyclin B1, cdc2, and p-cdc2 (T14). Meanwhile, YSY-01A could inhibit the TNF-α-induced NF-κB nuclear translocation and lead to the increase of IκBα as well as the decrease of IKK and Gadd45α. In conclusion, YSY-01A showed remarkable anti-cancer activity on SK-OV-3 cells, and its molecular mechanisms were related to G2/M cell cycle arrest.

Key words: Proteasome inhibitor, YSY-01A, SK-OV-3, Cell-cycle related protein, High content screening

中图分类号:

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Supporting:

Foundation items: Eleventh Five-Year Plan for National Science and Technology Major Project (Grant No. 2009ZX0930-010), National Science Foundation of China (Grant No. 81172915) and a grant from Major New Drugs Research and Development Platform of Peking University (Grant No. 2009ZX09301-010).#br# ^*Corresponding author. Tel.: 86-10-82802467, 86-10-82801504;

贾璇, 袁霞, 楚明明, 冉福香, 李润涛^*, 崔景荣^*. 新的蛋白酶体抑制剂YSY-01A对SK-OV-3细胞的周期阻滞作用[J]. 中国药学(英文版), DOI: 10.5246/jcps.2013.06.070.

Xuan Jia, Xia Yuan, Mingming Chu, Fuxiang Ran, Runtao Li^*, Jingrong Cui^*. Cell cycle arrest effect of compound YSY-01A, a new proteasome inhibitor, on SK-OV-3 cells[J]. Journal of Chinese Pharmaceutical Sciences, DOI: 10.5246/jcps.2013.06.070.

参考文献

[1] Fu, S.; Allen, T. Mol. Aspects Med. 2012, 33, 446-466.
[2] Robert, R.; Janine, K.; Isabel, L.; Julia, S.; Erika, M.; Aline, C.; Bettina, K.; Frank, H.; Gabriele, I.S.; Gaiping, W.; Klaus, E. Biochim. Biophys. Acta Gen. Subj. 2013, 1830, 2105-2117.
[3] Boyette-Davis, J.A.; Cata, J.P.; Zhang, H.; Driver, L.C.; Wenderlschafer-Crabb, G.; Kennedy, W.R.; Dougherty, P.M. Pain. 2011, 12, 1017-1024.
[4] Li, X.F.; Liu, S.T.; Huang, H.B.; Liu, N.N.; Zhao, C.; Liao, S.Y.; Yang, C.S.; Liu, Y.R.; Zhao, C.G.; Li, S.J.; Lu, X.Y.; Liu, C.J.; Guan, L.X.; Zhao, K.; Shi, X.Q.; Song, W.B.; Zhou, P.; Dong, X.X.; Guo, H.P.; Wen, C.Z.; Zhang, C.; Jiang, L.L.; Ma, N.F.; Li, B.; Wang, S.Q.; Tan, H.; Wang, X.J.; Dou, Q.P.; Liu, J.B. Cell Rep. 2013, 3, 211-222.
[5] Denis, S.; Benjamin, B.O.W.P.; Abdelouahid, E.K.; Helene, E.B.; Mutmid, A.; Foued, G.; Simeon, S.; Youssef, H.; Mohamed, H. Cell Signalling. 2013, 25, 308-318.
[6] Xin, D.; Yin, C.Z.; Ren, Y.J.; Qiu, P.X.; Jia, P.P.; Jing, W.; Shun, L.G.; Yu, L.W. J. Surg. Res. 2010, 162, 193-202.
[7] Fawzia, B.G.; Joan, O.; Andrew, L.; Jun, L.; Barbara, A.F.; Samuel, W.F. Exp. Mol. Pathol. 2011, 90, 123-130.
[8] Ling, L.; Cheng, Y.; Christian, H.; Rohit, S.; Gur, P.K. Biochem. Pharmacol. 2010, 79, 137-146.
[9] Bettina, E.; Michael, K.; Vladimir, W.; Edmund, M. Chem. Biol. Interact. 2011, 191, 239-249.
[10] Tong, K.; Liu, J.T.; Yuan, X.; Xu, B.; Guo, W.; Han, L.Q.; Yao, S.Y.; Ge, Z.M.; Li, R.T.; Cui, J.R. J. Chin. Pharm. Sci. 2012, 5, 448-458.
[11] Gasparri, F.; Cappella, P.; Galvani, A. J. Biomol. Screen. 2006, 11, 586-598.
[12] Sabine, V.; Robert, P.; Gilliane, M.; Yannick, A.; Catherine, J. Dev. Biol. (Amsterdam, Neth.). 2004, 267, 265-278.
[13] Will, R.R. Undergrad. Chem. Res. 2002, 1, 1-7.
[14] Connell, M.; Walworth, N.; Carr, A.M. Trends Cell Biol. 2000, 10, 296-303.
[15] Yan, X.L.; Xu, B.; Li, M.; Zhou, Y.; Cui, J.R. J. Chin. Pharm. 2009, 44, 904-908.
[16] Andrew, W.M. Cell. 2004, 116, 221-234.
[17] May, C.M.; Gilles, D.J. J. Mol. Biol. 1999, 286, 475-487.
[18] Catherine, G.T.; David, O.M. Curr. Opin. Cell Biol. 2000, 12, 658-665.
[19] Clute, P.; Pines, J. Nat. Cell Biol. 1999, 1, 82-87.
[20] Michael, W.M.; Newport, J. Science. 1998, 282, 1886-1889.
[21] Zheng, X.; Zhang, Y.; Chen, Y.Q.; Castranova, V.; Shi, X.; Chen, F. Biochem. Biophys. Res. Commun. 2005, 329, 95-99.
[22] Suzanne, M.R.; Joel, E.T.; Albert, S.B.Jr.; Liu, R.; Julian, A.; Peter, E.; James, C.C.Jr. Int. J. Radiat. Oncol. Biol. Phys. 2001, 50, 183-193.
[23] Concetta, C.; Raffaella, G.; Luana, A.; Gabriele, A.; Daniela, M.; Edvige, S.; Cristina, C.; Gabriella, A.; Ausilia, G.; Alessandra, R.; Gioacchin, I.; Ruggero, D.; Rosario, G.; Massimo, G.; Francesco, D.R. Leuk. Res. 2011, 35, 52-60.
[24] Xin, D.; Yin, C.Z.; Ren, Y.J.; Qiu, P.X.; Jia, P.P.; Jing, W.; Shun, L.G.; Yu, L.W. J. Surg. Res. 2010, 162, 193-202.
[25] Kearsey, J.M.; Coates, P.J.; Prescott, A.R.; Warbrick, E.; Hall, P.A. Oncogene. 1995, 11, 1675-1683.
[26] Des, R.R. Int. J. Biochem. Cell Biol. 2009, 41, 986-989.

新的蛋白酶体抑制剂YSY-01A对SK-OV-3细胞的周期阻滞作用

Cell cycle arrest effect of compound YSY-01A, a new proteasome inhibitor, on SK-OV-3 cells

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