Browsing by Author "Hiss, Donavon Charles"

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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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    Rutin as a potent antioxidant: implications for neurodegenerative disorders
    (Hindawi Publishing Corporation, 2018) Enogieru, Adaze Bijou; Haylett, William; Hiss, Donavon Charles; Bardien, Soraya; Ekpo, Okobi Eko
    A wide range of neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and prion diseases, share common mechanisms such as neuronal loss, apoptosis, mitochondrial dysfunction, oxidative stress, and inflammation. Intervention strategies using plant-derived bioactive compounds have been offered as a form of treatment for these debilitating conditions, as there are currently no remedies to prevent, reverse, or halt the progression of neuronal loss. Rutin, a glycoside of the flavonoid quercetin, is found in many plants and fruits, especially buckwheat, apricots, cherries, grapes, grapefruit, plums, and oranges. Pharmacological studies have reported the beneficial effects of rutin in many disease conditions, and its therapeutic potential in several models of NDs has created considerable excitement. Here, we have summarized the current knowledge on the neuroprotective mechanisms of rutin in various experimental models of NDs. The mechanisms of action reviewed in this article include reduction of proinflammatory cytokines, improved antioxidant enzyme activities, activation of the mitogen-activated protein kinase cascade, downregulation of mRNA expression of PD-linked and proapoptotic genes, upregulation of the ion transport and antiapoptotic genes, and restoration of the activities of mitochondrial complex enzymes. Taken together, these findings suggest that rutin may be a promising neuroprotective compound for the treatment of NDs.