Basic Medical Sciences

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Browsing Basic Medical Sciences 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
    (MDPI, 2024) Abrahams, Beynon; Gerber, Anthonie; Hiss, Donavon C.
    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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    Investigating the potential antiproliferative effect of 𝘔𝘰𝘳𝘪𝘯𝘨𝘢 𝘰𝘭𝘦𝘪𝘧𝘦𝘳𝘢 aqueous leaf extract in MCF-7 breast cancer cells
    (University of the Free State, 2023) Moremane, Malebogo M.; Tiloke, Charlette; Abrahams, Beynon
    𝗕𝗮𝗰𝗸𝗴𝗿𝗼𝘂𝗻𝗱: Breast cancer is associated with elevated mortality and morbidity rates in women across the world. Current chemotherapeutic drugs such as Doxorubicin (Dox) display contra-indications, thus expressing the need for alternative treatment methods. Therefore, to reduce the cancer burden, the study’s objective was to investigate whether an aqueous leaf extract of 𝘔𝘰𝘳𝘪𝘯𝘨𝘢 𝘰𝘭𝘦𝘪𝘧𝘦𝘳𝘢 (MO), a medicinal tree native to India and indigenous to Africa, possesses antiproliferative potential against MCF-7 breast cancer cells. 𝗠𝗲𝘁𝗵𝗼𝗱𝗼𝗹𝗼𝗴𝘆: In order to suppress cell growth, MCF-7 cells were treated with MO (2600 μg/ml) for 72 hours. Cells were also co-exposed with Dox (0.978 μM), modelled as a positive control. The unexposed cells served as the control. Biochemical analysis was conducted after 72 hours (MTT, GSH, DCFH-DA, ATP, Caspase 3/7, 8/9, qPCR and western blot assays) to assess the efficacy of MO and Dox. 𝗥𝗲𝘀𝘂𝗹𝘁𝘀: 𝘔𝘰𝘳𝘪𝘯𝘨𝘢 𝘰𝘭𝘦𝘪𝘧𝘦𝘳𝘢 aqueous leaf extract significantly reduced the proliferation of breast cancer cells by inducing oxidative stress through increasing ROS whilst decreasing glutathione content and Nrf2 protein expression. Additionally, MO induced apoptosis by increasing caspases -3/7, -8, -9, metabolic activity and upregulating p53. Similar results were observed in Dox-exposed cells. Furthermore, cell death due to MO was activated with downregulation of Bcl-2, PARP-1 and Bax. Dox decreased the growth of breast cancer cells by increasing ROS. In contrast, Dox induced chemoresistance through increased GSH content and downregulated apoptotic protein Bax and p53 gene. However, the MO + Dox combination induced antiproliferative potential similarly to MO, suggesting a possible synergistic effect. 𝗖𝗼𝗻𝗰𝗹𝘂𝘀𝗶𝗼𝗻: MO aqueous leaf extract displayed antiproliferative potential by inducing apoptosis and oxidative damage to the MCF-7 breast cancer cells