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In Vitro Cytotoxicity of Trastuzumab (Tz) and Se-Trastuzumab (Se-Tz) against the Her/2 Breast Cancer Cell Lines JIMT-1 and BT-474 |
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| Authors: | Priyanka Bapat Debalina Goswami Sewell Mallory Boylan Arun K Sharma Julian E Spallholz |
| Affiliation: | 1.Nutritional Sciences, College of Human Sciences, Texas Tech University, Lubbock, TX 79409, USA; (P.B.); (D.G.S.); (M.B.);2.Department of Pharmacology, Penn State Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA; |
| Abstract: | Her/2+ breast cancer accounts for ~25% mortality in women and overexpression of Her/2 leads to cell growth and tumor progression. Trastuzumab (Tz) with Taxane is the preferred treatment for Her/2+ patients. However, Tz responsive patients often develop resistance to Tz treatment. Herein, redox selenides (RSe-) were covalently linked to Tz using a selenium (Se)-modified Bolton–Hunter Reagent forming Seleno-Trastuzumab (Se-Tz; ~25 µgSe/mg). Se-Tz was compared to Tz and sodium selenite to assess the viability of JIMT-1 and BT-474 cells. Comparative cell viability was examined by microscopy and assessed by fluorometric/enzymatic assays. Se-Tz and selenite redox cycle producing superoxide (O2•−) are more cytotoxic to Tz resistant JIMT-1 and Tz sensitive BT-474 cells than Tz. The results of conjugating redox selenides to Tz suggest a wider application of this technology to other antibodies and targeting molecules. |
| Keywords: | human epidermal growth factor receptor 2 (Her/2) epidermal growth factor receptor (EGFR) selenium (Se) antibody drug conjugate (ADC) monoclonal antibody (mab) Herceptin® Trastuzumab (Tz) Kadcyla® (T-DM-1) superoxide (O2• − ) reduced glutathione (GSH) |