Abstract C100: Evaluation of pyriplatin, a monofunctional cationic platinum(II) compound, in human cancer cells

摘要: Background: We evaluated pyriplatin (cis‐diammine(pyridine)chloroplatinum(II) or cDPCP), a platinum‐based antitumor drug candidate, in vitro using an established cancer cell line panel (Ref. 1) with direct comparison to cisplatin and oxaliplatin. Pyriplatin is monofunctional, cationic compound proven anticancer properties mice 2) recently rediscovered as substrate for the organic cation transporters, hOCT1 hOCT2 3). Methods: Antiproliferative effects of given single agent 24 h were 10 human lines. Flow cytometry was used record cycle after staining cells propidium iodide study apopotosis imaged FITC‐conjugated annexin V. Effects combinations either taxol, gemcitabine, SN38, 5‐fluorouracil parallel corresponding Gene expression determined by quantitative RT‐PCR. The formation platinum‐DNA adducts over time ICP‐MS. Results: exhibited cytotoxic against lines treatment (IC50 values: 171 – 443 µM). continued be effective time, IC50 values decreasing µM 72 HOP‐62 cells, most sensitive line. also observed at short points, ranging from 230 450 1, 2 5 h. Combinations taxol showed better than additive antiproliferative effects. These results obtained both pretreatment prior simultaneous pyriplatin. on revealed accumulation sub‐G1, apoptotic phase, only hours treatment, which result unique that Increased apoptosis induction relative confirmed Annexin‐V. Quantitative RT‐PCR indicated high levels RAD50 mRNA are more resistant pyriplatin, suggesting role double‐strand breaks homologous recombination repair cellular response damage. Conclusions: those oxaliplatin, although potency roughly one order magnitude lower induces earlier oxaliplatin downstream DNA double strand evident cisplatin. Support: This work supported part grant U. S. National Cancer Institute. Citation Information: Mol Ther 2009;8(12 Suppl):C100.