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

Kim Hei-Man Chow; Raymond Wai-Yin Sun; Janice B.B. Lam; Carrie Ka-Lei Li; Aimin Xu; Dik-Lung Ma; Ruben Abagyan; Yu Wang; Chi-Ming Che

doi:10.1158/0008-5472.CAN-09-3324

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

Kim Hei-Man Chow
, Raymond Wai-Yin Sun
, Janice B.B. Lam
, Carrie Ka-Lei Li
, Aimin Xu
, Dik-Lung Ma
, Ruben Abagyan
, Yu Wang^*
, Chi-Ming Che^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Journal article › peer-review

98 Citations (Scopus)

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/β-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/β-catenin signaling.

Original language	English
Pages (from-to)	329–337
Number of pages	9
Journal	Cancer Research
Volume	70
Issue number	1
DOIs	https://doi.org/10.1158/0008-5472.CAN-09-3324
Publication status	Published - 1 Jan 2010

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10.1158/0008-5472.CAN-09-3324

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title = "A Gold(III) Porphyrin Complex with Antitumor Properties Targets the Wnt/β-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/β-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/β-catenin signaling.",

author = "Chow, \{Kim Hei-Man\} and Sun, \{Raymond Wai-Yin\} and Lam, \{Janice B.B.\} and Li, \{Carrie Ka-Lei\} and Aimin Xu and Dik-Lung Ma and Ruben Abagyan and Yu Wang and Chi-Ming Che",

note = "Funding Information: Grants from Seeding Funds for Basic Research of the University of Hong Kong (Y. Wang), Hong Kong Research Grant Council grants HKU 777908M (Y. Wang) and HKU 779707M (A. Xu), and the Area of Excellent Scheme AoE/P-10-01 established under University Grants Committee HKSAR (C. Che). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Publisher copyright: {\textcopyright} 2010 American Association for Cancer Research.",

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AU - Chow, Kim Hei-Man

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AU - Li, Carrie Ka-Lei

AU - Xu, Aimin

AU - Ma, Dik-Lung

AU - Abagyan, Ruben

AU - Wang, Yu

AU - Che, Chi-Ming

N1 - Funding Information: Grants from Seeding Funds for Basic Research of the University of Hong Kong (Y. Wang), Hong Kong Research Grant Council grants HKU 777908M (Y. Wang) and HKU 779707M (A. Xu), and the Area of Excellent Scheme AoE/P-10-01 established under University Grants Committee HKSAR (C. Che). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Publisher copyright: © 2010 American Association for Cancer Research.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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/β-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/β-catenin signaling.

AB - 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/β-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/β-catenin signaling.

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

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