Abstract | BACKGROUND: Enhanced removal of cisplatin- DNA adducts has been reported as one of main causes of cell resistance to cisplatin. This particular resistance mechanism may be circumvented by platinum complexes that bind differently to DNA. One line of work is focussed on trans platinum complexes, some of which exhibit antitumour activity similar to or even higher than that of their cis counterparts. METHODS: RESULTS: In the present work we examined the mechanisms induced by these compounds to cause tumour cells toxicity. We have found that these compounds induced a complete blockade at the S phase of the cell cycle inhibiting total mRNA transcription and precluding p53 activation. CONCLUSION: In contrast to other DNA-damaging agents, these compounds do not induce senescence-associated permanent arrest. Furthermore, only a small percentage of these cells enter into apoptosis, with most of the population dying by a necrosis-like mechanism.
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Authors | V Cepero, B García-Serrelde, V Moneo, F Blanco, A M González-Vadillo, A Alvarez-Valdés, C Navarro-Ranninger, A Carnero |
Journal | Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
(Clin Transl Oncol)
Vol. 9
Issue 8
Pg. 521-30
(Aug 2007)
ISSN: 1699-048X [Print] Italy |
PMID | 17720655
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Ligands
- Organometallic Compounds
- Organoplatinum Compounds
- RNA, Messenger
- dichloro(cyclohexylamine)(dimethylamine)platinum(II)
- dihydroxo(cyclohexylamine)(dimethylamine)platinum(II)
- DNA
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Topics |
- Antineoplastic Agents
(chemical synthesis, pharmacology, toxicity)
- Apoptosis
- Cell Cycle
- Cell Line, Tumor
- Cellular Senescence
- DNA
(biosynthesis)
- Dose-Response Relationship, Drug
- Humans
- Ligands
- Necrosis
- Organometallic Compounds
(chemical synthesis, pharmacology, toxicity)
- Organoplatinum Compounds
(chemical synthesis, pharmacology, toxicity)
- RNA, Messenger
(metabolism)
- Transcription, Genetic
(drug effects)
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