Research Articles (Basic Medical Sciences)
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Item Open Access 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.Item Open Access Moringa oleifera and autophagy: evidence from in vitro studies on chaperone-mediated autophagy in HepG₂ Cancer cells(Taylor and Francis Group, 2023) Bopape, Matlola; Tiloke, Charlette; Ntsapi, ClaudiaHepatocellular carcinoma (HCC) is the most prevalent primary liver cancer in Sub-Saharan African countries, including South Africa (SA). Given the limitations in current HCC therapeutics, there is an increasing need for alternative adjuvant therapeutic options. As such, several cell survival mechanisms, such as autophagy, have been identified as potential adjuvant therapeutic targets in HCC treatment. Of the three most established autophagic pathways, the upregulation of chaperone-mediated autophagy (CMA) has been extensively described in various cancer cells, including HCC cells. CMA promotes tumor growth and chemotherapeutic drug resistance, thus contributing to HCC tumorigenesis. Therefore, the modulation of CMA serves as a promising adjuvant target for current HCC therapeutic strategies. Phytochemical extracts found in the medicinal plant, Moringa oleifera (MO), have been shown to induce apoptosis in numerous cancer cells, including HCC. MO leaves have the greatest abundance of phytochemicals displaying anticancer potential. However, the potential interaction between the pro-apoptotic effects of MO aqueous leaf extract and the survival-promoting role of CMA in an in vitro model of HCC remains unclear. This review aims to summarize the latest findings on the role of CMA, and MO in the progression of HCC.