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Modulation of gold(III) porphyrin 1a-induced apoptosis by mitogen-activated protein kinase signaling pathways
Wang Y.1; He Q.-Y.2; Che C.-M.1; Tsao S.W.3; Sun R.W.-Y.1; Chiu J.-F.3
2008-03-15
Source PublicationBiochemical Pharmacology
ISSN00062952
Volume75Issue:6Pages:1282-1291
Abstract

Gold(III) porphyrin 1a is a novel gold(III) complex with selective anticancer effect in a number of human carcinoma cell lines. We have previously shown that gold(III) porphyrin 1a mediated mitochondrial transmembrane potential (ΔΨ) depletion, leading to cytochrome c release, nucleus translocation of apoptosis-inducing factor (AIF), and generation of reactive oxygen species (ROS). The current study addressed gold(III) porphyrin 1a-induced phosphoproteome alterations and modulation of cell death by the mitogen-activated protein kinase (MAPK) family proteins. ERK and p38 were transiently activated upon gold(III) porphyrin 1a treatment. Inhibition of p38 phosphorylation rescued gold(III) porphyrin 1a-induced cell death upstream of caspase activation. Attenuation of ΔΨ was the primary effect of gold(III) porphyrin 1a leading to p38 phosphorylation. Further functional proteomic study suggested that differential regulation of phosphotyrosine proteins were related to p38 activation in gold(III) porphyrin 1a-induced signal transduction cascade. In summary, p38 modulated gold(III) porphyrin 1a-induced cell death downstream of mitochondria, and phosphorylation of multiple proteins also involved in this process. These results suggested that gold(III) porphyrin 1a is a promising anticancer agent directed toward the mitochondria. © 2007 Elsevier Inc. All rights reserved.

KeywordApoptosis Gold(Iii) Compound Mapk Mitochondria Proteomics Tyrosine Phosphorylation
DOI10.1016/j.bcp.2007.11.024
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000254687800004
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Cited Times [WOS]:36   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorHe Q.-Y.; Chiu J.-F.
Affiliation1.Department of Chemistry and Open Laboratory of Chemical Biology, The University of Hong Kong, Hong Kong SAR, China
2.Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China
3.Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China
Recommended Citation
GB/T 7714
Wang Y.,He Q.-Y.,Che C.-M.,et al. Modulation of gold(III) porphyrin 1a-induced apoptosis by mitogen-activated protein kinase signaling pathways[J]. Biochemical Pharmacology,2008,75(6):1282-1291.
APA Wang Y.,He Q.-Y.,Che C.-M.,Tsao S.W.,Sun R.W.-Y.,&Chiu J.-F..(2008).Modulation of gold(III) porphyrin 1a-induced apoptosis by mitogen-activated protein kinase signaling pathways.Biochemical Pharmacology,75(6),1282-1291.
MLA Wang Y.,et al."Modulation of gold(III) porphyrin 1a-induced apoptosis by mitogen-activated protein kinase signaling pathways".Biochemical Pharmacology 75.6(2008):1282-1291.
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