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

Priyanka Bapat, Debalina Goswami Sewell, Mallory Boylan, Arun K. Sharma, Julian E. Spallholz

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number4655
JournalInternational journal of molecular sciences
Volume22
Issue number9
DOIs
StatePublished - 2021

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 (O)
  • Trastuzumab (Tz)

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