Abstract：
:The antineoplastic potential of a new stable mixed phosphine gold(I) complex containing tris(tert-butyl)phosphine (tBu3P) and bis(diphenylphosphino)ethene (dppet), namely [Au(tBu3P)(dppet)Cl], has been investigated in the human colon cancer HCT-116 cell line. The (31)P NMR solution study, confirms the structural features observed in the solid state and, in addition, indicates partial formation of dinuclear cationic [Au(tBu3P)2](+) and [Au(dppet)2](+) species. The ionic character and strong Au-P bonds of this gold(I) species are similar to those of the most active antitumor gold compounds so far studied. The title compound was found to exhibit strong cytotoxicity, showing 85 fold greater toxicity than cisplatin (IC50=0.45μM vs IC50=39.16 for cisplatin at 24h) on the HCT-116 line. The cytotoxic effects were, at least partly, mediated by the induction of apoptotic cell death as evidenced by the sub-G1 cell accumulation, oligonucleosomal DNA fragmentation, caspase-3 activation and the release of cytochrome c from the mitochondria. The gold(I) compound showed little interaction with DNA measured through fluorescence quenching studies with calf thymus DNA. The inhibitory effect of the gold(I) compound on intracellular redox proteins has been also observed in pretreated HCT-116 cells. The compound was particularly effective in inhibiting thioredoxin reductase, that is likely responsible for the increased ROS production, and subsequent apoptosis induction via the mitochondrial pathway.
journal_name
J Inorg Biochemjournal_title
Journal of inorganic biochemistryauthors
Lupidi G,Avenali L,Bramucci M,Quassinti L,Pettinari R,Khalife HK,Gali-Muhtasib H,Marchetti F,Pettinari Cdoi
10.1016/j.jinorgbio.2013.03.014subject
Has Abstractpub_date
2013-07-01 00:00:00pages
78-87eissn
0162-0134issn
1873-3344pii
S0162-0134(13)00072-Xjournal_volume
124pub_type
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journal_title：Journal of inorganic biochemistry
pub_type： 杂志文章,评审
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更新日期：2006-05-01 00:00:00
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更新日期：2009-05-01 00:00:00
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pub_type： 杂志文章
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journal_title：Journal of inorganic biochemistry
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更新日期：2014-11-01 00:00:00
