title: A gold(III) porphyrin complex with antitumor properties targets the Wnt/beta-catenin pathway.
abstract: Gold(III) complexes have shown promise as antitumor agents, but their clinical usefulness has been limited by their poor stability under physiological conditions. A novel gold(III) porphyrin complex [5-hydroxyphenyl-10,15,20-triphenylporphyrinato gold(III) chloride (gold-2a)] with improved aqueous stability showed 100-fold to 3,000-fold higher cytotoxicity than platinum-based cisplatin and IC50 values in the nanomolar range in a panel of human breast cancer cell lines. Intraductal injections of gold-2a significantly suppressed mammary tumor growth in nude mice. These effects are attributed, in part, to attenuation of Wnt/beta-catenin signaling through inhibition of class I histone deacetylase (HDAC) activity. These data, in combination with computer modeling, suggest that gold-2a may represent a promising class of anticancer HDAC inhibitor preferentially targeting tumor cells with aberrant Wnt/beta-catenin signaling.
authors.affiliation: Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Kim Hei-Man
authors.initials: KH
authors.lastname: Chow
authors.forename: Raymond Wai-Yin
authors.initials: RW
authors.lastname: Sun
authors.forename: Janice B B
authors.initials: JB
authors.lastname: Lam
authors.forename: Carrie Ka-Lei
authors.initials: CK
authors.lastname: Li
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Dik-Lung
authors.initials: DL
authors.lastname: Ma
authors.forename: Ruben
authors.initials: R
authors.lastname: Abagyan
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Che
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005260:Female; D017612:Gold Compounds / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D020128:Inhibitory Concentration 50; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D013058:Mass Spectrometry; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D017612:Gold Compounds; D056572:Histone Deacetylase Inhibitors; D008665:Metalloporphyrins; D051153:Wnt Proteins; D051176:beta Catenin