NDLI: Gallium phosphinoarylbisthiolato complexes counteract drug resistance of cancer cells

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Metallomics Vol - 6 Issue - 3

Metallomics Vol - 6 Issue - 2

Gallium phosphinoarylbisthiolato complexes counteract drug resistance of cancer cells

Content Provider	Royal Society of Chemistry (RSC)
Author	Tudoran, Lucian Barbu Ilea, Petru Hey-Hawkins, Evamarie Virag, Piroska Krausz, Ludovic Tibor Vălean, Ana-Maria Lupan, Iulia Fischer-Fodor, Eva Tatomir, Corina Imre-Lucaci, Florica Silaghi-Dumitrescu, Luminita Schrepler, Maria Perde Precup, Calin George
Copyright Year	2014
Abstract	In cancer therapy the platinum-based drugs are used frequently with a good clinical outcome, but besides unwanted side effects which occur, the tumour cells subjected to treatment are prone to develop tolerance or even multidrug resistance (MDR). Metal compounds with a central atom other than platinum are efficient in targeting the chemoresistant cells, therefore the biological outcome of two recently synthesized gallium phosphinoarylbisthiolato complexes was studied, having the formula [X][Ga{PPh(2-SC6H4)2-κ3S,S′,P}{PPh(2-SC6H4)2-κ2S,S′}] where [X] is either the NEt3H (1) or PPh4 (2) cation. Compounds 1 and 2 display in vitro cytotoxicity against both platinum-sensitive and platinum-resistant cell lines (A2780 and A2780cis). Morphological and ultrastructural evidence points toward their capacity to impair tumour cells survival. This behaviour is based on malignant cells capacity to selectively intake gallium, and to bind to the cellular DNA. They are able to cause massive DNA damage in treated cancer cells, focusing on 7-methylguanine and 8-oxoguanine sites and oxidizing the pyrimidine bases; this leads to early apoptosis of a significant percent of treated cells. The intrinsic and extrinsic apoptotic pathways are influenced through the modulation of gene expression following the treatment with complexes 1 and 2, which accompanies the negative regulation of P-glycoprotein 1 (Pgp-1), an important cellular ABC-type transporter from the multidrug resistance (MDR) family. The studied Ga(III) compounds demonstrated the capacity to counteract the chemoresistance mechanisms in the tumours defiant to standard drug action. Compound 2 shows a good anticancer potential and it could represent an alternative to platinum-based drugs especially in the situation of standard treatment failure.
Starting Page	833
Ending Page	844
Page Count	12
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	6
Issue Number	4
Journal	Metallomics
DOI	10.1039/c3mt00278k
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Gallium Ion Cytotoxicity Pyrimidine P-glycoprotein Gene DNA 8-Oxoguanine MDR 6-O-Methylguanine Cancer Multiple drug resistance Apoptosis
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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