title: Anticancer Gold(III) Porphyrins Target Mitochondrial Chaperone Hsp60.
abstract: Identification of the molecular target(s) of anticancer metal complexes is a formidable challenge since most of them are unstable toward ligand exchange reaction(s) or biological reduction under physiological conditions. Gold(III) meso-tetraphenylporphyrin (gold-1 a) is notable for its high stability in biological milieux and potent in vitro and in vivo anticancer activities. Herein, extensive chemical biology approaches employing photo-affinity labeling, click chemistry, chemical proteomics, cellular thermal shift, saturation-transfer difference NMR, protein fluorescence quenching, and protein chaperone assays were used to provide compelling evidence that heat-shock protein 60 (Hsp60), a mitochondrial chaperone and potential anticancer target, is a direct target of gold-1 a in vitro and in cells. Structure-activity studies with a panel of non-porphyrin gold(III) complexes and other metalloporphyrins revealed that Hsp60 inhibition is specifically dependent on both the gold(III) ion and the porphyrin ligand.
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Center, and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong.
authors.forename: Di
authors.initials: D
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Center, and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong.
authors.forename: Yungen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Center, and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong.
authors.forename: Yau-Tsz
authors.initials: YT
authors.lastname: Lai
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Center, and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong.
authors.forename: Ka-Chung
authors.initials: KC
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Center, and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong.
authors.forename: Yi-Man
authors.initials: YM
authors.lastname: Fung
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Center, and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong.
authors.forename: Chun-Nam
authors.initials: CN
authors.lastname: Lok
authors.affiliation: State Key Laboratory of Synthetic Chemistry, Chemical Biology Center, and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, Hong Kong. cmche@hku.hk.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Che
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000187:drug effects*; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D018834:Chaperonin 60; D011166:Porphyrins; D006046:Gold
keywords: Hsp60; antitumor agents; biological targets; chemical proteomics; gold porphyrins