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• W2153666475 abstract "Abstract Purpose: This study aims to identify a novel therapeutic agent for head and neck cancer and to evaluate its antitumor efficacy. Experimental Design: A cell-based and phenotype-driven high-throughput screening of ∼2,400 biologically active or clinically used compounds was done using a tetrazolium-based assay on FaDu (hypopharyngeal squamous cancer) and NIH 3T3 (untransformed mouse embryonic fibroblast) cells, with secondary screening done on C666-1 (nasopharyngeal cancer) and GM05757 (primary normal human fibroblast) lines. The “hit” compound was assayed for efficacy in combination with standard therapeutics on a panel of human cancer cell lines. Furthermore, its mode of action (using transmission electron microscopy and flow cytometry) and its in vivo efficacy (using xenograft models) were evaluated. Results: Benzethonium chloride was identified as a novel cancer-specific compound. For benzethonium (48-hour incubation), the dose required to reduce cell viability by 50% was 3.8 μmol/L in FaDu, 42.2 μmol/L in NIH 3T3, 5.3 μmol/L in C666-1, and 17.0 μmol/L in GM05757. In vitro, this compound did not interfere with the effects of cisplatin, 5-fluorouracil, or γ-irradiation. Benzethonium chloride induced apoptosis and activated caspases after 12 hours. Loss of mitochondrial membrane potential (ΔΨM) preceded cytosolic Ca2+ increase and cell death. In vivo, benzethonium chloride ablated the tumor-forming ability of FaDu cells, delayed the growth of xenograft tumors, and combined additively with local tumor radiation therapy. Evaluation of benzethonium chloride on the National Cancer Institute/NIH Developmental Therapeutics Program 60 human cancer cell lines revealed broad-range antitumor activity. Conclusions: This high-throughput screening identified a novel antimicrobial compound with significant broad-spectrum anticancer activity." @default.
• W2153666475 created "2016-06-24" @default.
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• W2153666475 date "2006-09-15" @default.
• W2153666475 modified "2023-10-12" @default.
• W2153666475 title "Benzethonium Chloride: A Novel Anticancer Agent Identified by Using a Cell-Based Small-Molecule Screen" @default.
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• W2153666475 doi "https://doi.org/10.1158/1078-0432.ccr-06-0536" @default.
• W2153666475 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17000693" @default.
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