title: Apoptosis induced by 1,3,6,7-tetrahydroxyxanthone in Hepatocellular carcinoma and proteomic analysis.
abstract: Gamboge 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 β-tubulin and translationally controlled tumor protein were decreased while the 14-3-3σ and P16 protein expressions were up-regulated. In addition, TTA suppressed tumorigenesis partially through P16-pRb signaling. 14-3-3σ 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 14-3-3σ.
authors.affiliation: Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong, People's Republic of China.
authors.forename: Wei-ming
authors.initials: WM
authors.lastname: Fu
authors.forename: Jin-fang
authors.initials: JF
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Hong-sheng
authors.initials: HS
authors.lastname: Tan
authors.forename: Wei-mao
authors.initials: WM
authors.lastname: Wang
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.forename: Tak-ming
authors.initials: TM
authors.lastname: Chan
authors.forename: Ching-man
authors.initials: CM
authors.lastname: Tse
authors.forename: Kwong-sak
authors.initials: KS
authors.lastname: Leung
authors.forename: Gang
authors.initials: G
authors.lastname: Lu
authors.forename: Hong-xi
authors.initials: HX
authors.lastname: Xu
authors.forename: Hsiang-fu
authors.initials: HF
authors.lastname: Kung
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism; D005095:Exoribonucleases; D029760:Garcinia / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D034622:RNA Interference; D015398:Signal Transduction; D044004:Xanthones / Q000494:pharmacology*
chemical_list: C575656:1,3,6,7-tetrahydroxyxanthone; D048948:14-3-3 Proteins; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004365:Drugs, Chinese Herbal; D020543:Proteome; D044004:Xanthones; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human