ArticleThe Journal of biological chemistry2005
Combination of 5-fluorouracil and N1,N11-diethylnorspermine markedly activates spermidine/spermine N1-acetyltransferase expression, depletes polyamines, and synergistically induces apoptosis in colon carcinoma cells.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 53 citations in OpenAlex.
- 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
- Inhibition of autophagy enhances DENSpm-induced apoptosis in human colon cancer cells in a p53 independent manner.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- Combination of Fe/Cu -chelators and docosahexaenoic acid: an exploration for the treatment of colorectal cancer.Oncotarget · 2017Article
- KAP-1 is overexpressed and correlates with increased metastatic ability and tumorigenicity in pancreatic cancer.Medical oncology (Northwood, London, England) · 2014Article
- Polyamines and cancer: implications for chemotherapy and chemoprevention.Expert reviews in molecular medicine · 2013Review
- Overexpression of SSAT by DENSPM treatment induces cell detachment and apoptosis in glioblastoma.Oncology reports · 2012Article
- Article
- Role of polyamines in determining the cellular response to chemotherapeutic agents: modulation of protein kinase CK2 expression and activity.Molecular and cellular biochemistry · 2011Article
- DFMO: targeted risk reduction therapy for colorectal neoplasia.Best practice & research. Clinical gastroenterology · 2011Review
- 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.Cancer chemotherapy and pharmacology · 2011Article
- Characterization of the cell growth inhibitory effects of a novel DNA-intercalating bipyridyl-thiourea-Pt(II) complex in cisplatin-sensitive and -resistant human ovarian cancer cells.Investigational new drugs · 2011Article
- The role of the polyamine catabolic enzymes SSAT and SMO in the synergistic effects of standard chemotherapeutic agents with a polyamine analogue in human breast cancer cell lines.Cancer chemotherapy and pharmacology · 2010Article
- Insulin-like growth factor binding protein-3 has dual effects on gastrointestinal stromal tumor cell viability and sensitivity to the anti-tumor effects of imatinib mesylate in vitro.Molecular cancer · 2009Article
- Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer.Cancer research · 2009Article
- The novel polyamine analogue CGC-11093 enhances the antimyeloma activity of bortezomib.Cancer research · 2008Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The thymidylate synthase inhibitor 5-fluorouracil (5-FU) is used widely for chemotherapy of colorectal carcinoma. Recent studies showed that 5-FU affects polyamine metabolism in colon carcinoma cells. We therefore examined whether combinations of 5-FU with drugs that specifically target polyamine metabolism, i.e. N1,N11-diethylnorspermine (DENSPM) or alpha-difluoromethylornithine (DFMO), have synergistic effects in killing HCT116 colon carcinoma cells with wild-type or absent p53. Our results showed that simultaneous 5-FU and DENSPM, a spermine analogue, synergistically increased transcript levels of the polyamine catabolism enzyme spermidine/spermine N1-acetyltransferase, depleted spermine and spermidine, increased acetylated spermidine, and produced synergistic tumor cell apoptosis in both p53 wild-type and p53-null variants. By contrast, simultaneous combination of 5-FU with DFMO, an inhibitor of the polyamine biosynthetic enzyme ornithine decarboxylase, depleted putrescine but did not produce synergistic cell killing. Some pre-treatment and post-treatment regimens of DENSPM and DFMO were antagonistic to 5-FU depending on cellular p53 status. Protein and transcriptome expression analysis showed that combined 5-FU and DENSPM treatment activated caspase 9, but not caspase 3, and significantly suppressed NADH dehydrogenases and cytochrome c oxidases, consistent with the observed increase in hydrogen peroxide, loss of mitochondrial membrane potential, and release of cytochrome c. Our findings demonstrate the importance of the polyamine pathway in 5-FU effects and suggest that the combination of 5-FU with DENSPM has potential for development as therapy for colorectal carcinoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.