Fu, Wei-MingWei-MingFuZhang, Jin-FangJin-FangZhangWang, HuaHuaWangTan, Hong-ShengHong-ShengTanWang, Wei-MaoWei-MaoWangChen, Shih-ChiShih-ChiChenZhu, XiaoXiaoZhuChan, Tak-MingTak-MingChanTse, Ching-ManChing-ManTseProf. LEUNG Kwong SakLu, GangGangLuXu, Hong-XiHong-XiXu2023-03-172023-03-172012Apoptosis , 2012, vol. 17(8), pp. 842-8511573675Xhttp://hdl.handle.net/20.500.11861/7521Gamboge is a traditional Chinese medicine and our previous study showed that gambogic acid and gambogenic acid suppress the proliferation of HCC cells. In the present study, another active component, 1,3,6,7-tetrahydroxyxanthone (TTA), was identified to effectively suppress HCC cell growth. In addition, our Hoechst-PI staining and flow cytometry analyses indicated that TTA induced apoptosis in HCC cells. In order to identify the targets of TTA in HCC cells, a two-dimensional gel electrophoresis was performed, and proteins in different expressions were identified by MALDA-TOF MS and MS/ MS analyses. In summary, eighteen proteins with different expressions were identified in which twelve were up-regulated and six were down-regulated. Among them, the four most distinctively expressed proteins were further studied and validated by western blotting. The b-tubulin and translationally controlled tumor protein were decreased while the 14-3-3r and P16 protein expressions were up-regulated. In addition, TTA suppressed tumorigenesis partially through P16-pRb signaling. 14-3-3r silence reversed the suppressive effect of cell growth and apoptosis induced by introducing TTA. In conclusion, TTA effectively suppressed cell growth through, at least partially, up-regulation of P16 and 14-3-3r. © Springer Science+Business Media, LLC 2012.enApoptosis1 3 6 7-TetrahydroxyxanthoneP16Hepatocellular Carcinoma14-3-3σPeer Reviewed Journal Article10.1007/s10495-012-0729-y