A Gold(III) Porphyrin Complex with Antitumor Properties Targets the Wnt/β-catenin Pathway

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 1; pp. 329 - 337
• Main Authors: CHOW, Kim Hei-Man, SUN, Raymond Wai-Yin, LAM, Janice B. B, LI, Carrie Ka-Lei, AIMIN XU, MA, Dik-Lung, ABAGYAN, Ruben, YU WANG, CHE, Chi-Ming
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 2010
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; beta Catenin - drug effects; Biological and medical sciences; Cell Line, Tumor; Female; Gold Compounds - pharmacology; Histone Deacetylase Inhibitors - pharmacology; Humans; Immunoprecipitation; Inhibitory Concentration 50; Mammary Neoplasms, Experimental - drug therapy; Mass Spectrometry; Medical sciences; Metalloporphyrins - pharmacology; Mice; Mice, Nude; Pharmacology. Drug treatments; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Tumors; Wnt Proteins - drug effects; Xenograft Model Antitumor Assays; Antineoplastic agent; Protein wnt; Target; Gold complex; Targeting; Porphyrin; β Catenin; Porphyrin derivatives
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-09-3324

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.