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Asplatin enhances drug efficacy by altering the cellular response

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Metallomics Vol - 8 Issue - 6

Metallomics Vol - 8 Issue - 5

Metallomics Vol - 8 Issue - 4

Metallomics Vol - 8 Issue - 3

Metallomics Vol - 8 Issue - 2

Asplatin enhances drug efficacy by altering the cellular response

Content Provider	Royal Society of Chemistry (RSC)
Author	Wang, Hongxia Shi, Hongdong Liu, Yangzhong Cheng, Qinqin Wang, Jun
Copyright Year	2016
Abstract	Aspirin, a widely used anti-inflammatory drug, has been shown to be effective for the prevention and remission of cancers (Science, 2012, 337(21) 1471–1473). Asplatin, a Pt(IV) prodrug of cisplatin with the ligation of aspirin (c,c,t-[PtCl2(NH3)2(OH)(aspirin)]), demonstrates significantly higher cytotoxicity than cisplatin towards tumor cells and almost fully overcomes the drug resistance of cisplatin resistant cells. In this work, we have studied the molecular mechanism of asplatin by investigating the cellular response to this compound in order to understand the prominent inhibitory effect on the proliferation of cancer cells. The apoptosis analyses and the related gene expression measurements show that aspirin released from asplatin significantly modulates the cellular response to the platinum agent. Asplatin promotes the apoptosis via the BCL-2 associated mitochondrial pathway. The down-regulation of BCL-2 along with the up-regulation of BAX and BAK enhances the mitochondrial outer membrane permeability, resulting in the cytochrome c release from mitochondria into the cytosol. This event promotes the apoptosis by activation of caspase processing. Consequently, the ligation of aspirin significantly enhances the drug efficacy of the platinum complex in the low micromolar range. The alteration of the cellular response is probably responsible for the circumvention of the cisplatin resistance by asplatin. These results provide an insight into the mechanism of asplatin and provide information for designing new classic platinum drugs.
Starting Page	672
Ending Page	678
Page Count	7
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	8
Issue Number	7
Journal	Metallomics
DOI	10.1039/c6mt00066e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Bcl-2 Aspirin Cell membrane Caspase Cytotoxicity Prodrug The Alteration Cytosol Cisplatin Mitochondrion Ammonia Gene Covalent bond BAX Cancer Apoptosis
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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Asplatin enhances drug efficacy by altering the cellular response

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