Journal of Cancer Therapy最新文献

{"title":"Epirubicin-[Anti-HER2/<i>neu</i>] Synthesized with an Epirubicin-(C₁₃-<i>imino</i>)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium.","authors":"Cody P Coyne,&nbsp;Toni Jones,&nbsp;Andrzej Sygula,&nbsp;John Bailey,&nbsp;Lesya Pinchuk","doi":"10.4236/jct.2011.21004","DOIUrl":"https://doi.org/10.4236/jct.2011.21004","url":null,"abstract":"<p><strong>Purpose: </strong>Discover the anti-neoplastic efficacy of epirubicin-(C₁₃-imino)-[anti-HER2/neu] against chemotherapeutic-resistant SKBr-3 mammary carcinoma and delineate the capacity of selenium to enhance it's cytotoxic anti-neoplastic potency.</p><p><strong>Methods: </strong>In molar excess, EMCH was combined with epirubicin to create a covalent epirubicin-(C₁₃-imino)-EMCH-maleimide intermediate with sulfhydryl-reactive properties. Monoclonal immunoglobulin selective for HER2/neu was then thiolated with 2-iminothiolane at the terminal ε-amine group of lysine residues. The sulfhydryl-reactive epirubicin-(C₁₃-imino)-EMCH intermediate was then combined with thiolated anti-HER2/neu monoclonal immunoglobulin. Western-blot analysis was utilized to characterize the molecular weight profiles while binding of epirubicin-(C₁₃-imino)-[anti-HER2/neu] to membrane receptors was determined by cell-ELISA utilizing populations of SKBr-3 mammary carcinoma that highly over-expresses HER2/neu complexes. Anti-neoplastic potency of epirubicin-(C₁₃-imino)-[anti-HER2/neu] between the epirubicin-equivalent concentrations of 10^-12 M and 10^-7 M was determined by vitality staining analysis with and without the presence of selenium (5 μM).</p><p><strong>Results: </strong>Epiribucin-(C₁₃-imino)-[anti-HER2/neu] between epirubicin-equivalent concentrations of 10^-8 M to 10^-7 M consistently evoked higher anti-neoplastic potency than \"free\" non-conjugated epirubicin which corresponded with previous investigations utilizing epirubicin-(C₃-amide)-[anti-HER2/neu] and epirubicin-(C₃-amide)-[anti-EGFR]. Selenium at 5 mM consistently enhanced the cytotoxic anti-neoplastic potency of epirubicin-(C13-imino)-[anti-HER2/neu] at epirubicin equivalent concentrations (10-12 to 10-7 M).</p><p><strong>Conclusions: </strong>Epirubicin-(C₁₃-imino)-[anti-HER2/neu] is more potent than epirubicin against chemotherapeutic-resistant SKBr-3 mammary carcinoma and selenium enhances epirubicin-(C₁₃-imino)-[anti-HER2/neu] potency. The methodology applied for synthesizing epirubicin-(C₁₃-imino)-[anti-HER2/neu] is relatively time convenient and has low instrumentation requirements.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"2 1","pages":"22-39"},"PeriodicalIF":0.0,"publicationDate":"2011-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517615/pdf/nihms703263.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33885314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GREEN TEA POLYPHENOLS MEDIATED APOPTOSIS IN INTESTINAL EPITHELIAL CELLS BY A FADD-DEPENDENT PATHWAY.","authors":"Helieh S Oz, Jeffrey L Ebersole","doi":"10.4236/jct.2010.13018","DOIUrl":"10.4236/jct.2010.13018","url":null,"abstract":"<p><p>Colorectal cancer is the most common malignant complication in patients with chronic inflammatory bowel disease (IBD). In addition, these patients are at risk for developing painful complications during chemotherapy due to cytotoxic effects of drugs currently in use. Past studies have suggested a protective effect of tea consumption on gastrointestinal (GI) malignancies. Green tea polyphenols (GrTP) inhibited carcinogen-induced GI tumors in rodents and induced apoptosis in various carcinoma cell lines. We hypothesized that GrTP and its polyphenolic compounds regulate apoptosis in the intestinal epithelia. In this study, the effects of GrTP and its polyphenolics on apoptosis was evaluated in intestinal epithelial, IEC-6, cells grown to 85% confluency. GrTP (400-800 mg/ml) induced DNA fragmentation in a dose dependent fashion. Higher concentrations (>800 mg/ml) induced a mixed apoptosis and cytolysis. Epithelial cells exposed to GrTP and a major polyphenol, EGCG, but not EGC or EC, increased caspase activities in a time and dose dependent manner. The caspase inhibitors rescued cells from GrTP and EGCG-induced cell death. Concomitantly, GrTP resulted in activation of fatty acid synthase (Fas)-associated protein with death domain (FADD) and recruitment to Fas/CD95 domain 30 minutes following treatment. While GrTP also blocked NF-κB activation, an NFκ-B inhibitor (MG132) only promoted cytolysis. In conclusion, these data demonstrated GrTP and EGCG induced apoptosis in intestinal epithelia mediated by caspase-8 through a FADD dependent pathway. Future investigation may warrant preventive as well as therapeutic strategies for GrTP in GI malignancy.</p>","PeriodicalId":15267,"journal":{"name":"Journal of Cancer Therapy","volume":"1 3","pages":"105-113"},"PeriodicalIF":0.0,"publicationDate":"2010-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115755/pdf/nihms264463.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30250051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}