title: Anti-tumour effects of xanthone derivatives and the possible mechanisms of action.
abstract: To explore the potential anti-tumour activities of xanthone derivatives, 26 hydroxylxanthones and benzoxanthones and their structurally modified analogues were examined for potential cytotoxic activities against eight human cancer cell lines. Most of the xanthone derivatives exhibited a higher degree of cytotoxicity on HepG2 cells than on the other seven cancer cell lines. Compound 24 (1,3,7-Trihydroxy-12H-benzo[b] xanthen-12-one) showed the highest degree of cytotoxicity of the tested compounds against HepG2 cells and demonstrated good tumour specificity by exhibiting a much higher degree of cytotoxicity against HepG2 cells than against normal liver cells (L02). Several valuable structure-activity relationships were derived from the cytotoxicity data. In addition, we found that compound 24 could downregulate the expression of the Mcl-1 protein, induce changes in the mitochondrial membrane potential and induce apoptosis in HepG2 cells via the mitochondrial pathway. Compound 24 was also shown to inhibit topoisomerase (topo) II activity and downregulate the levels of both topo II mRNA and protein in HepG2 cells. The present results suggest that due to its potent cytotoxicity and good tumour selectivity, compound 24 may be exploited as a potential lead compound in the development of a new anti-tumour agent with specific activity against liver cancer.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, People's Republic of China.
authors.forename: Quan-Guan
authors.initials: QG
authors.lastname: Su
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Cai
authors.forename: Yue-Li
authors.initials: YL
authors.lastname: Sun
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Li-Jian
authors.initials: LJ
authors.lastname: Xian
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D044004:Xanthones; D004250:DNA Topoisomerases, Type II