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Titolo:
A cycloplatinated compound of p-isopropylbenzaldehyde thiosemicarbazone and its chloro-bridged derivative induce apoptosis in cis-DDP resistant cellswhich overexpress the H-ras oncogene
Autore:
Perez, JM; Quiroga, AG; Montero, EI; Alonso, C; Navarro-Ranninger, C;
Indirizzi:
UnivnAutonoma Madrid, Fac Ciencias, Dept Quim Inorgan, E-28049 Madrid, Spai Univ Autonoma Madrid Madrid Spain E-28049 Inorgan, E-28049 Madrid, Spai Univ9Autonoma Madrid, Fac Ciencias, Ctr Biol Mol Severo Ochoa, CSIC, E-2804 Univ Autonoma Madrid Madrid Spain E-28049 Mol Severo Ochoa, CSIC, E-2804
Titolo Testata:
JOURNAL OF INORGANIC BIOCHEMISTRY
fascicolo: 4, volume: 73, anno: 1999,
pagine: 235 - 243
SICI:
0162-0134(19990415)73:4<235:ACCOPT>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTICANCER AGENTS; CISPLATIN; ACTIVATION; DEATH; MECHANISMS; LEUKEMIA; DRUGS; DNA;
Keywords:
cis-DDP; cyclometallated compounds; cytotoxicity; apoptosis; H-ras;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Navarro-Ranninger, C Univ Autonoma Madrid, Fac Ciencias, Dept Quim Inorgan, Cantoblanco, E-28049 Univ Autonoma Madrid Cantoblanco Madrid Spain E-28049
Citazione:
J.M. Perez et al., "A cycloplatinated compound of p-isopropylbenzaldehyde thiosemicarbazone and its chloro-bridged derivative induce apoptosis in cis-DDP resistant cellswhich overexpress the H-ras oncogene", J INORG BIO, 73(4), 1999, pp. 235-243

Abstract

cis-Diamminedichloroplatinum(II) (cis-DDP) is a widely used antitumour drug which produces important damage on the DNA inducing apoptosis in several cell lines. We have analysed the cytotoxic activity of novel cyclometallated complexes of p-isopropylbenzaldehyde thiosemicarbazone (p-is.TSCN) and their dimeric chloro-bridged derivatives in murine keratinocytes transformed by the H-ras oncogene which are resistant to cis-DDP (Pam-ras cells). The data show that, in contrast with cis-DDP, the tetrameric cycloplatinated complex [Pt(p-is.TSCN)](4) and its dimeric chloro-bridged derivative [Pt( mu Cl) (p-is.TSCN)], have a good in vitro therapeutic index when comparing the cytotoxicity in Pam-ras cells to normal murine keratinocytes (Pam 212 cells) since they induce cell death in Pam-ras cells at drug concentrations significantly lower than those needed to kill Pam 212 cells. At equitoxic doses(IC90), both complexes produce characteristic features of apoptosis in Pam-ras cells together with a drastic decrease in levels of H-ras protein. These effects are not observed when the cells are treated with the IC90 of thecis-DDP drug nor the p-is.TSCN ligand. Altogether, these results suggest that the platinum compounds [Pt(p-is.TSCN)](4) and [Pt(mu Cl) (p-is.TSCN)](2) might have potential as antitumour agents in view of their specific induction of apoptosis in cis-DDP resistant cells. (C) 1999 Elsevier Science Inc. All rights reserved.

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Documento generato il 29/03/20 alle ore 01:32:47