Inhibition of the proteasome activity by gallium(III) complexes contributes to their anti prostate tumor effects.

Inhibition of the proteasome activity by gallium(III) complexes contributes to their anti prostate tumor effects. Research Abstract Details 

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Inhibition of the proteasome activity by gallium(III) complexes contributes to their anti prostate tumor effects. Abstract Text:

Di Chen,Michael Frezza,Rajendra Shakya,Qiuzhi Cindy Cui,Vesna Milacic,Claudio N Verani,Q Ping Dou,

The investigation of metal-based complexes with potential antitumor activity has been of paramount importance in recent years due to the successful use of cisplatin against various cancers. Gallium(III) and subsequently developed gallium(III)-containing complexes have shown promising antineoplastic effects when tested in a host of malignancies, specifically in lymphomas and bladder cancer. However, the molecular mechanism responsible for their anticancer effect is yet to be fully understood. We report here for the first time that the proteasome is a molecular target for gallium complexes in a variety of prostate cancer cell lines and in human prostate cancer xenografts. We tested five gallium complexes (1-5) in which the gallium ion is bound to an NN'O asymmetrical ligand containing pyridine and substituted phenolate moieties in a 1:2 (M/L) ratio. We found that complex 5 showed superior proteasome inhibitory activity against both 26S proteasome (IC50, 17 micromol/L) and purified 20S (IC50, 16 micromol/L) proteasome. Consistently, this effect was associated with apoptosis induction in prostate cancer cells. Additionally, complex 5 was able to exert the same effect in vivo by inhibiting growth of PC-3 xenografts in mice (66%), which was associated with proteasome inhibition and apoptosis induction. Our results strongly suggest that gallium complexes, acting as potent proteasome inhibitors, have a great potential to be developed into novel anticancer drugs.

Inhibition of the proteasome activity by gallium(III) complexes contributes to their anti prostate tumor effects. Publishing Authors By Initials

D Chen,M Frezza,R Shakya,QC Cui,V Milacic,CN Verani,QP Dou,

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Inhibition of the proteasome activity by gallium(III) complexes contributes to their anti prostate tumor effects. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 67

Page Numbers: 9258-65

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Oct

YEAR: 2007

Inhibition of the proteasome activity by gallium(III) complexes contributes to their anti prostate tumor effects. Information

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LANGUAGE: eng

NlmUniqueID: 2984705

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Grant and Affiliation Information for Inhibition of the proteasome activity by gallium(III) complexes contributes to their anti prostate tumor effects.

AFFILIATION: The Prevention Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA.

Country: United States

AGENCY: United States NCI

GRANT: 1R01CA120009

ACRONYM: CA

MEDLINETA: Cancer Res

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