Anti-Neoplastic Cytotoxicity of Gemcitabine-(C4-amide)-[anti-EGFR] in Dual-combination with Epirubicin-(C3-amide)-[anti-HER2/neu] against Chemotherapeutic-Resistant Mammary Adenocarcinoma (SKBr-3) and the Complementary Effect of Mebendazole.
{"title":"Anti-Neoplastic Cytotoxicity of Gemcitabine-(C<sub>4</sub>-<i>amide</i>)-[anti-EGFR] in Dual-combination with Epirubicin-(C<sub>3</sub>-<i>amide</i>)-[anti-HER2/<i>neu</i>] against Chemotherapeutic-Resistant Mammary Adenocarcinoma (SKBr-3) and the Complementary Effect of Mebendazole.","authors":"C P Coyne, Toni Jones, Ryan Bear","doi":"10.17303/jcrto.2014.203","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Delineate the feasibility of simultaneous, dual selective \"targeted\" chemotherapeutic delivery and determine if this molecular strategy can promote higher levels anti-neoplastic cytotoxicity than if only one covalent immunochemotherapeutic is selectively \"targeted\" for delivery at a single membrane associated receptor over-expressed by chemotherapeutic-resistant mammary adenocarcinoma.</p><p><strong>Methodology: </strong>Gemcitabine and epirubicin were covalently bond to anti-EGFR and anti-HER2/<i>neu</i> utilizing a rapid multi-phase synthetic organic chemistry reaction scheme. Determination that 96% or greater gemcitabine or epirubicin content was covalently bond to immunoglobulin fractions following size separation by micro-scale column chromatography was established by methanol precipitation analysis. Residual binding-avidity of gemcitabine-(C<sub>4</sub>-<i>amide</i>)-[anti-EG-FR] applied in dual-combination with epirubicin-(C<sub>3</sub>-<i>amide</i>)-[anti-HER2/<i>neu</i>] was determined by cell-ELIZA utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) populations. Lack of fragmentation or polymerization was validated by SDS-PAGE/immunodetection/chemiluminescent autoradiography. Anti-neoplastic cytotoxic potency was determined by vitality stain analysis of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) monolayers known to uniquely over-express EGFR (2 × 10<sup>5</sup>/cell) and HER2/<i>neu</i> (1 × 10<sup>6</sup>/cell) receptor complexes. The covalent immunochemotherapeutics gemcitabine-(C<sub>4</sub>-<i>amide</i>)-[anti-EGFR] and epirubicin-(C<sub>3</sub>-<i>amide</i>)-[anti-HER2/<i>neu</i>] were applied simultaneously in dual-combination to determine their capacity to collectively evoke elevated levels of anti-neoplastic cytotoxicity. Lastly, the tubulin/microtubule inhibitor mebendazole evaluated to determine if it's potential to complemented the anti-neoplastic cytotoxic properties of gemcitabine-(C4-<i>amide</i>)-[anti-EGFR] in dual-combination with epirubicin-(C<sub>3</sub>-<i>amide</i>)-[<i>anti-HER2/neu</i>].</p><p><strong>Results: </strong>Dual-combination of gemcitabine-(C<sub>4</sub>-<i>amide</i>)-[anti-EGFR] with epirubicin-(C<sub>3</sub>-<i>amide</i>)-[anti-HER2/<i>neu</i>] produced greater levels of anti-neoplastic cytotoxicity than either of the covalent immunochemotherapeutics alone. The benzimidazole microtubule/tubulin inhibitor, mebendazole complemented the anti-neoplastic cytotoxicity of gemcitabine-(C<sub>4</sub>-<i>amide</i>)-[anti-EGFR] in dual-combination with epirubicin-(C<sub>3</sub>-<i>amide</i>)-[<i>anti-HER2/neu</i>].</p><p><strong>Conclusions: </strong>The dual-combination of gemcitabine-(C<sub>4</sub>-<i>amide</i>)-[anti-EGFR] with epirubicin-(C<sub>3</sub>-<i>amide</i>)-[anti-HER2/<i>neu</i>] produced higher levels of selectively \"targeted\" anti-neoplastic cytotoxicity against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) than either covalent immunochemotherapeutic alone. The benzimidazole tubulin/microtubule inhibitor, mebendazole also possessed anti-neoplastic cytotoxicity against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) and complemented the potency and efficacy of gemcitabine-(C<sub>4</sub>-<i>amide</i>)-[anti-EGFR] in dual-combination with epirubicin-(C<sub>3</sub>-<i>amide</i>)-[<i>anti-HER2/neu</i>].</p>","PeriodicalId":15189,"journal":{"name":"Journal of Cancer Research and Therapeutic Oncology","volume":"2 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2014-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381351/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cancer Research and Therapeutic Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.17303/jcrto.2014.203","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Aims: Delineate the feasibility of simultaneous, dual selective "targeted" chemotherapeutic delivery and determine if this molecular strategy can promote higher levels anti-neoplastic cytotoxicity than if only one covalent immunochemotherapeutic is selectively "targeted" for delivery at a single membrane associated receptor over-expressed by chemotherapeutic-resistant mammary adenocarcinoma.
Methodology: Gemcitabine and epirubicin were covalently bond to anti-EGFR and anti-HER2/neu utilizing a rapid multi-phase synthetic organic chemistry reaction scheme. Determination that 96% or greater gemcitabine or epirubicin content was covalently bond to immunoglobulin fractions following size separation by micro-scale column chromatography was established by methanol precipitation analysis. Residual binding-avidity of gemcitabine-(C4-amide)-[anti-EG-FR] applied in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu] was determined by cell-ELIZA utilizing chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) populations. Lack of fragmentation or polymerization was validated by SDS-PAGE/immunodetection/chemiluminescent autoradiography. Anti-neoplastic cytotoxic potency was determined by vitality stain analysis of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) monolayers known to uniquely over-express EGFR (2 × 105/cell) and HER2/neu (1 × 106/cell) receptor complexes. The covalent immunochemotherapeutics gemcitabine-(C4-amide)-[anti-EGFR] and epirubicin-(C3-amide)-[anti-HER2/neu] were applied simultaneously in dual-combination to determine their capacity to collectively evoke elevated levels of anti-neoplastic cytotoxicity. Lastly, the tubulin/microtubule inhibitor mebendazole evaluated to determine if it's potential to complemented the anti-neoplastic cytotoxic properties of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu].
Results: Dual-combination of gemcitabine-(C4-amide)-[anti-EGFR] with epirubicin-(C3-amide)-[anti-HER2/neu] produced greater levels of anti-neoplastic cytotoxicity than either of the covalent immunochemotherapeutics alone. The benzimidazole microtubule/tubulin inhibitor, mebendazole complemented the anti-neoplastic cytotoxicity of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu].
Conclusions: The dual-combination of gemcitabine-(C4-amide)-[anti-EGFR] with epirubicin-(C3-amide)-[anti-HER2/neu] produced higher levels of selectively "targeted" anti-neoplastic cytotoxicity against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) than either covalent immunochemotherapeutic alone. The benzimidazole tubulin/microtubule inhibitor, mebendazole also possessed anti-neoplastic cytotoxicity against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) and complemented the potency and efficacy of gemcitabine-(C4-amide)-[anti-EGFR] in dual-combination with epirubicin-(C3-amide)-[anti-HER2/neu].
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
