ArticleCancer chemotherapy and pharmacology2011
Combination effects of platinum drugs and N1, N11 diethylnorspermine on spermidine/spermine N1-acetyltransferase, polyamines and growth inhibition in A2780 human ovarian carcinoma cells and their oxaliplatin and cisplatin-resistant variants.
Article in Cancer chemotherapy and pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis.International journal of molecular sciences · 2024Review
- The Polyamine Analogue Ivospemin Increases Chemotherapeutic Efficacy in Murine Ovarian Cancer.Biomedicines · 2024Article
- Polyamines in Ovarian Aging and Disease.International journal of molecular sciences · 2023Review
- c-MYC-Driven Polyamine Metabolism in Ovarian Cancer: From Pathogenesis to Early Detection and Therapy.Cancers · 2023Review
- Spermine oxidase induces DNA damage and sensitizes fusion negative rhabdomyosarcoma cells to irradiation.Frontiers in cell and developmental biology · 2023Article
- Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms.Frontiers in chemistry · 2023Review
- The Association between Spermidine/Spermine NInternational journal of molecular sciences · 2022Review
- Hyaluronate-coated perfluoroalkyl polyamine prodrugs as bioactive siRNA delivery systems for the treatment of peritoneal cancers.Biomaterials advances · 2022Article
- Polyamine metabolism and cancer: treatments, challenges and opportunities.Nature reviews. Cancer · 2018Review
- Self-immolative nanoparticles for simultaneous delivery of microRNA and targeting of polyamine metabolism in combination cancer therapy.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- Article
- Self-immolative polycations as gene delivery vectors and prodrugs targeting polyamine metabolism in cancer.Molecular pharmaceutics · 2015Article
- Polyamine pathway inhibition as a novel therapeutic approach to treating neuroblastoma.Frontiers in oncology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeTo understand the mechanisms behind platinum drug/DENSPM-induced inhibition of cancer cell growth, we compared the effects of oxaliplatin and cisplatin when combined with DENSPM on the induction of SSAT mRNA, activity, polyamines and cell growth in A2780 human ovarian carcinoma cells and their oxaliplatin- and cisplatin-resistant variants A2780/C10B and A2780/CP, respectively.
methodsParental and Pt-resistant cells were treated with platinum agent alone, DENSPM alone or combination (10 μM each, 20 h). QRT-PCR, radioactive product measurement and HPLC were used for mRNA, activity and polyamine pools, respectively; drug interaction on cell growth was by SRB and isobologram analysis.
resultsBoth platinum agents induced SSAT mRNA in parental A2780 cells, but not in resistant cells. Platinum drug/DENSPM combinations produced high levels of SSAT activity in parental cells with significant depletion of spermine and spermidine, but not in resistant cells. Co-treatment with platinum agents increased the levels of DENSPM in all cell lines. Oxaliplatin/DENSPM combination was superior to cisplatin/DENSPM in the inhibition of cell growth in parental cells. No synergy was observed in the resistant cells.
conclusionsIncreased DENSPM levels following co-treatment with Pt agents enhances the translation and stability of SSAT protein leading to polyamine pool depletion, facilitating more Pt-DNA adduct formation in parental cells. Oxaliplatin/DENSPM combination is superior to cisplatin/DENSPM in cell growth inhibition as DACH-Pt DNA adducts are cytotoxic even at relatively fewer numbers. Reduced platinum uptake in Pt-resistant cells contributes to reduced SSAT mRNA induction and absence of synergy when combined with DENSPM.
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