In vitro cytotoxicity of trastuzumab (Tz) and se-trastuzumab (se-tz) against the her/2 breast cancer cell lines jimt-1 and bt-474

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.

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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. cc-by

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Keywords

Antibody drug conjugate (ADC), Epidermal growth factor receptor (EGFR), Herceptin®, Human epidermal growth factor receptor 2 (Her/2), Kadcyla® (T-DM-1), Monoclonal antibody (mab), Reduced glutathione (GSH), Selenium (Se), Superoxide (O2•−), Trastuzumab (Tz)

Citation

Bapat, P., Sewell, D.G., Boylan, M., Sharma, A.K., & Spallholz, J.E.. 2021. In vitro cytotoxicity of trastuzumab (Tz) and se-trastuzumab (se-tz) against the her/2 breast cancer cell lines jimt-1 and bt-474. International Journal of Molecular Sciences, 22(9). https://doi.org/10.3390/ijms22094655

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