ArticleNeoplasia (New York, N.Y.)2009
Using acetaminophen's toxicity mechanism to enhance cisplatin efficacy in hepatocarcinoma and hepatoblastoma cell lines.
Article in Neoplasia (New York, N.Y.), 2009. 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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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- High-Dose Acetaminophen as a Treatment for Cancer.Livers · 2024Article
- High-Dose Acetaminophen with Concurrent CYP2E1 Inhibition Has Profound Anticancer Activity without Liver Toxicity.The Journal of pharmacology and experimental therapeutics · 2024Article
- High-Dose Acetaminophen withCancers · 2023Article
- Interactions of Analgesics with Cisplatin: Modulation of Anticancer Efficacy and Potential Organ Toxicity.Medicina (Kaunas, Lithuania) · 2021Review
- High dose acetaminophen inhibits STAT3 and has free radical independent anti-cancer stem cell activity.Neoplasia (New York, N.Y.) · 2021Article
- Blocking LPA-dependent signaling increases ovarian cancer cell death in response to chemotherapy.Redox biology · 2018Article
- Preclinical high-dose acetaminophen with N-acetylcysteine rescue enhances the efficacy of cisplatin chemotherapy in atypical teratoid rhabdoid tumors.Pediatric blood & cancer · 2014Article
- Acetaminophen enhances cisplatin- and paclitaxel-mediated cytotoxicity to SKOV3 human ovarian carcinoma.Anticancer research · 2013Article
- Article
- Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2012Review
- Hydroxyethyl disulfide as an efficient metabolic assay for cell viability in vitro.Toxicology in vitro : an international journal published in association with BIBRA · 2012Article
- In-depth identification of pathways related to cisplatin-induced hepatotoxicity through an integrative method based on an informatics-assisted label-free protein quantitation and microarray gene expression approach.Molecular & cellular proteomics : MCP · 2012Article
- The interconnectedness of cancer cell signaling.Neoplasia (New York, N.Y.) · 2011Article
- Dinosaurs and ancient civilizations: reflections on the treatment of cancer.Neoplasia (New York, N.Y.) · 2010Article
- The War on Cancer rages on.Neoplasia (New York, N.Y.) · 2009Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND/
aimsAcetaminophen overdose causes hepatotoxicity mediated by toxic metabolites generated through the cytochrome P450 enzyme. The objective of this study was to investigate whether acetaminophen (AAP) can enhance cisplatin (CDDP) cytotoxicity against human hepatocarcinoma and hepatoblastoma cells in vitro and whether this effect can be prevented by N-acetylcysteine (NAC).
methodsIn vitro studies (glutathione [GSH] level, cell viability, and immunoblot assays) were performed using human hepatocarcinoma and hepatoblastoma cells cultured in AAP, CDDP, and the combination of both with or without delayed NAC administration. The pharmacology and toxicology of high-dose AAP in rats were also examined.
resultsAcetaminophen decreased GSH levels in liver cancer cells in a dose- and time-dependent manner. Acetaminophen combined with CDDP had enhanced cytotoxicity over CDDP alone. The cytotoxicity caused by AAP plus CDDP was decreased by NAC, with the effectiveness being time-dependent. The GSH level was lowered in the liver but not in the blood or the brain in rats treated with a high dose of AAP (1000 mg/kg). The expression of CYP2E1 protein, a key cytochrome P450 enzyme, varies among species but is not correlated to AAP sensitivity in liver cancer cells.
conclusionsOur results suggest that a chemotherapeutic regimen containing both AAP and CDDP with delayed NAC rescue has the potential to enhance chemotherapeutic efficacy while decreasing adverse effects. This would be a promising approach particularly for hepatoblastomas regardless of cellular CYP2E1 protein level but could also be beneficial in other malignancies.
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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.