Department of Medical BioSciences

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https://hdl.handle.net/10566/76
The department fields specific expertise within the broad research fields of Anatomy, Cardiovascular Physiology, Herbal Sciences, Immunology, Medical Microbiology, Molecular & Cell Biology, Neuroscience, Reproduction, Toxicology and Virology

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Browsing by Author "Abrahams, Beynon"

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    Combination treatment with EGFR Inhibitor and doxorubicin synergistically inhibits proliferation of MCF-7 cells and MDA-MB-231 triple-negative breast cancer cells in vitro
    (Multidisciplinary Digital Publishing Institute (MDPI), 2024) Abrahams, Beynon; Hiss, Donavon Charles; Gerber, Anthonie
    The role of the epidermal growth factor receptor (EGFR) in tumor progression and survival is often underplayed. Its expression and/or dysregulation is associated with disease advancement and poor patient outcome as well as drug resistance in breast cancer. EGFR is often overexpressed in breast cancer and particularly triple-negative breast cancer (TNBC), which currently lacks molecular targets. We examined the synergistic potential of an EGFR inhibitor (EGFRi) in combination with doxorubicin (dox) in estrogen-positive (ER+) MCF-7 and MDA-MB-231 TNBC cell lines. The exposure of MDA-MB-231 and MCF-7 to EGFRi produced an IC50s of 6.03 µM and 3.96 µM, respectively. Dox induced MDA-MB-231 (IC50 9.67 µM) and MCF-7 (IC50 1.4 µM) cytotoxicity. Combinations of EGFRi-Dox significantly reduced the IC50 in MCF-7 (0.46 µM) and MBA-MB 231 (0.01 µM). Synergistic drug interactions in both cell lines were confirmed using the bliss independence model. Pro-apoptotic caspase-3/7 activation occurred in MCF-7 at 0.1–10 µM of EGFRi and dox single treatments, whilst 1 μM dox yielded a more potent effect on MDA-MB-231. EGFRi and Dox individually and in combination downregulated the EGFR gene expression in MCF-7 and MDA-MB-231 (p < 0.001). This study demonstrates EGFRi’s potential for eliciting synergistic interactions with dox, causing enhanced growth inhibition, apoptosis induction, and downregulation of EGFR in both cell lines.
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    The effects of various combinations of different classes of anticancer drugs and tyrosine kinase inhibitors on the human MCF-7 breast carcinoma cell line
    (University of the Western Cape, 2014) Abrahams, Beynon; Hiss, D.C.; Abdul-Rasool, Sahar
    This study investigated the effects of TKIs on the growth and proliferation of MCF-7 breast carcinoma cells in culture. MCF-7 cells were exposed to different concentrations of TKIs alone and in combination with each other. Inhibition of cell growth by TKIs used individually occurred in a dose- and time-dependent manner. When EGFR Inhibitor I, EGFR Inhibitor II/BIBX1382 and the multi-specific EGFR/ErbB-2/ErB-4 Inhibitor were used in combination with each other at equimolar log dose concentrations, the combined effects on cell growth was significantly different to inhibitors used individually as reflected in a decreased EC50 (IC50) during combination treatments. Generally, for the combinations with DOX, CPL and the TKIs, synergistic as well as antagonistic effects were observed at isoeffective concentrations with resultant decreases in dose reduction indices (DRIs) implying greater efficacies with the respective combinations. In this study, conventional PCR was used to detect and illustrate the presence of the EGFR gene in the samples, while RT-qPCR was used to determine the mRNA expression levels of this gene in MCF-7 breast carcinoma cells