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

doi:10.5246/jcps.2013.06.070

Abstract

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

CLC Number:

R962','1');return false;" target="_blank"> R962

Supporting:

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.

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