Department of Physiological Sciences

Permanent URI for this community

https://scholar.sun.ac.za/handle/10019.1/232

Browse

Browsing Department of Physiological Sciences by browse.metadata.advisor "Africander, Donita"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    A comparison of compounded-bioidentical hormone formulations versus FDA-approved hormone formulations in breast cancer progression
    (Stellenbosch : Stellenbosch University, 2023-03) Mochoele, Kamano Angela; Engelbrecht, Anna-Mart; Africander, Donita; Du Plessis, Manisha; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.
    ENGLISH ABSTRACT: Introduction: Oestrogen and oestrogen receptor-induced signalling plays an important role in breast cancer development and progression. Studies have shown that certain menopausal hormone therapies {MHTs} containing oestrogens and oestrogens in combination with progestogens, increase the risk of invasive breast cancer. Compounded-bioidentical hormone therapies {cBHTs}, not FDA-approved or regulated by the Medicines Control Council of South Africa, have become a popular MHT and are advertised as safer efficient alternatives. Oestrogen alone and in combination with progestogens such as medroxyprogesterone acetate {MPA} and norethindrone {NET} enhance breast cell proliferation, migration and invasion. lt is therefore important to determine the effects of compounded oestrogen formulations in the development and progression of breast cancer. This study aims to provide a comparative profile of the effects of traditional menopausal therapies {estrone + MPA and estrone + NETA}, an FDA-approved bioidentical formulation {oestradiol + progesterone {bE2+bP4}} with the compounded bioidentical biest hormone formulation E2 + estriol {bE2+bE3} on the progression of breast cancer. Methods: Human ER+ mammary adenocarcinoma cells {MCF7} were used. Proliferation was assessed by determining the cell viability through water-soluble tetrazolium salt {WST-1} assays. The cell cycle was analysed with flow cytometry. Western blot analyses were performed to assess the proliferation marker MCM2, the Pl3K/Akt signalling pathway and epithelial-to-mesenchymal transition {EMT} markers; E-cadherin, N-cadherin, Snail and β-catenin. Migration was measured through a wound healing assay. Results and discussion: All treatment combinations significantly increased cancer cell viability. The cell cycle analysis shows that FDA-approved estrone + MPA and estrone + NETA treatments induced the accumulation of MCF7 cells in the GO/Gl phase of the cell cycle. Western blot analysis revealed that all hormone treatments did not activate the Pl3K/Akt pathway. Furthermore, treatment of BE2 + BP4 indicated mesenchymal characteristics of EMT. The wound closure assay showed that the hormone treatments did not induce migration. Conclusion: According to our findings, there are both similarities and differences among the compounded biest combinations and FDA-approved hormone formulations. Concerningly, cBHT increases cell viability in a manner consistent with the FDA-approved formulations. Similar to FDA- approved therapies, they did not cause migration or activate the Akt pathway for cell proliferation. In contrast, when compared to their FDA-approved counterparts, cBHT formulations exhibited different effects on EMT and the cell cycle. All together these results demonstrate that cBHT treatments did not stimulate the pathways associated with breast cancer progression that was stimulated by the FDA-approved formulations. Future recommendations include investigating the effects of cBHT preparations on other pathways involved in breast cancer initiation and progression in comparison to the FDA-approved formulations.
  • Thumbnail Image
    Item
    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.