Browsing by Author "Van der Merwe, Michelle"

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    Melatonin incorporation into hormone replacement therapy: a potential strategy to decrease breast cancer risk?
    (Stellenbosch : Stellenbosch University, 2022-12) Van der Merwe, Michelle; Engelbrecht, Anna-Mart; Du Plessis, Manisha; Africander, Donita; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Background: Breast cancer remains a leading cause of cancer-related death among women worldwide and in South Africa, and cancer cases are expected to increase. Estrogen has been identified as a carcinogen that increases the risk for cancer development and promotes tumour progression. Estrogen-containing hormone replacement therapy (HRT) has been shown to increase breast cancer risk resulting in a decline in HRT use. Subsequently, safer alternatives such as bio-identical HRT and the incorporation of melatonin into HRT have been increasingly considered and investigated. The safety of bio-identical HRT has, however, not been established. Additionally, the mechanisms by which melatonin attenuates estrogen- induced carcinogenic effects remain to be fully elucidated. Therefore, this study aims to compare the effects of a commercially available bio-identical 17β-estradiol (E2) standard and a pharmaceutical bio-identical E2 on breast cancer hallmarks. Furthermore, it aims to compare whether melatonin addition to E2 or bE2 reduces estrogen-induced cancer progression. Methods: The ER+ breast adenocarcinoma MCF-7 cell line was treated with estrogen and/or melatonin for 72 hours. The effect of treatments on various cancer hallmarks was investigated. Cell viability was assessed using a WST-1 assay. Cell signalling regulatory proteins PTEN, Akt, and ERK were assessed by western blot analysis. The cell proliferation marker, MCM-2, was assessed with western blot analysis and immunocytochemistry, and the apoptotic markers, caspase-7, and PARP were assessed with western blot analysis. Additionally, cell migration was assessed with a migration assay, and epithelial-to- mesenchymal transition markers, E-cadherin, and Snail were assessed with western blot analysis. Results: E2 and bE2 increased cell viability similarly, whereas melatonin inhibited cell viability. The combination of melatonin with E2 or bE2 inhibited estrogen-induced cell viability to levels comparable to control. Both E2 and bE2 increased cell migration and reduced the epithelial marker, E-cadherin expression. Interestingly, the addition of melatonin to bE2, but not to E2, reduced cell migration. Conclusion: These results agree with the existing literature regarding the pro-tumourigenic effects exerted by estrogen, confirming the risks associated with HRT. The incorporation of melatonin into HRT or as an adjuvant to cancer therapy might be beneficial in counteracting estrogen-induced viability and migration.