Antitumor-Activity of Orally-Administered Ammine Amine Platinum (Iv) Dicarboxylate Complexes Against a Panel of Human Ovarian-Carcinoma Xenografts

Tumour-inhibiting platinum complexes—state of the art and future perspectives

“…Furthermore, loss of mismatch repair does not confer resistance to JM-216 . However, the general pattern of response across cell lines and human ovarian carcinoma xenografts is similar to cisplatin and carboplatin (Kelland et al 1993a(Kelland et al , 1993b.…”

Carboxylation of Kinetically Inert Platinum(IV) Hydroxy Complexes. An Entr.acte.ee into Orally Active Platinum(IV) Antitumor Agents

“…(OC-6-43)-Amminedichloro(cyclohexanamine)bis((methyIsulfonyl)acetato-O)platinum(rV) (22). Add a solution of 1 g (5.8 mmol) of 3-chloroperoxybenzoic acid (MCPBA) in 10 mL of CH2C12 to a stirred, nitrogen-purged suspension of 0.344 g (0.58 mmol) of 21 cooled to 0 °C.…”

Cellular Uptake, DNA Binding and Apoptosis Induction of CytotoxicTrans‐[PtCl2(N,N‐dimethylamine)(Isopropylamine)] in A2780cisROvarian Tumor Cells

“…indicates that the cells were preincubated for 24 hours with 50 txM of L-buthionine sulfoximine in order to After a 24 hours treatment period with equitoxic doses (2xlC50) of cis-DDP, trans-DDP and trans-[PtCl(N,N-dimethylamine)(isopropylamine)], there was a greater cell detachment from the culture plate surface in A2780 cells compared with A2780cisR cells, as revealed by phase contrast microscopy (data not showaa). Cell detachment has been previously reported as an indication of apoptosis induction [ 11,12]. Both detached and attached cells were mixed and assayed by a flow cytometric annexin V binding assay [24].…”

“…These results are in agreement with previously reported data, which showed that trans-[PtCl2(N,N-dimethylamine) (isopropylamine)] is also able to circumvent cisplatin resistance and induces apoptosis in Pam 212-ras murine keratinocytes [ 10,11 ]. It has been reported that the A2780cisR human ovarian tumor cell line e.xhibits acquired resistance to cis-DDP from a combination of decreased uptake, enhanced DNA repair/tolerance and elevated GSH levels [12,13]. The aim of the present study was to investigate whether the cellular uptake, the reaction with GSH and the level ot platinum binding to DNA of trans-[PtC12(N,N-dimethylamine)(isopropylamine)] may help to understand the mechamsm(s) by which this drug overcomes cisplatin resistance.…”