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dc.contributor.authorPerez, JM
dc.contributor.authorKelland, LR
dc.contributor.authorMontero, EI
dc.contributor.authorBoxall, FE
dc.contributor.authorFuertes, MA
dc.contributor.authorAlonso, C
dc.contributor.authorNavarro-Ranninger, C
dc.date.accessioned2018-09-17T08:21:18Z
dc.date.issued2003-04
dc.identifier4
dc.identifier.citationMOLECULAR PHARMACOLOGY, 2003, 63 pp. 933 - 944
dc.identifier.issn0026-895X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2686
dc.identifier.doi10.1124/mol.63.4.933
dc.description.abstractThe antitumor and cellular pharmacological properties of the trans-Pt(IV) complex, trans-[PtCl2(OH)(2)(dimethylamine)(isopropylamine)] (compound 2) has been evaluated in comparison with its corresponding trans-Pt(II) counterpart, trans-[PtCl2(dimethylamine)(isopropylamine)] (compound 1). The results reported here indicate that compound 2 markedly circumvents cisplatin resistance in 41 McisR and CH1 cisR ovarian tumor cell lines endowed with different mechanisms of resistance (decreased platinum accumulation and enhanced DNA repair/tolerance, respectively). However, compound 1 is able to circumvent cisplatin resistance only in CH1 cisR cells. Interestingly, at equitoxic concentrations, compounds 1 and 2 induce a higher amount of apoptotic cells than cisplatin in CH1 cisR cells. Moreover, the number of apoptotic cells induced by compounds 1 and 2 correlates with their ability to form DNA interstrand cross-links in CH1cisR cells. Although compounds 1 and 2 showed remarkable cytotoxic activity, only compound 2 was able to inhibit the growth of CH1 human ovarian carcinoma xenografts in mice. Binding studies with serum albumin indicate that compound 1 possesses a much higher reactivity against albumin than compound 2. Moreover, the level of binding of compound 1 to plasma proteins during the period 15 min to 1 h after administration to mice (15 mg/kg, i.p.) is 2.5-fold higher than that of compound 2. Therefore, the lack of in vivo antitumor activity shown by compound 1 might be related to its extracellular inactivation before reaching the tumor site because of its high rate of binding to plasma proteins.
dc.format.extent933 - 944
dc.languageeng
dc.language.isoeng
dc.titleAntitumor and cellular pharmacological properties of a novel platinum(IV) complex: trans-[PtCl2(OH)(2)(dimethylamine)(isopropylamine)]
dc.typeJournal Article
rioxxterms.versionofrecord10.1124/mol.63.4.933
rioxxterms.licenseref.startdate2003-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMOLECULAR PHARMACOLOGY
pubs.notesunique-id: ISI:000181854200020
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume63
pubs.embargo.termsNot known
dc.contributor.icrauthorKelland, Lloyden


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