A comparison of compounded-bioidentical hormone formulations versus FDA-approved hormone formulations in breast cancer progression

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dc.contributor.advisorEngelbrecht, Anna-Marten_ZA
dc.contributor.advisorAfricander, Donitaen_ZA
dc.contributor.advisorDu Plessis, Manishaen_ZA
dc.contributor.authorMochoele, Kamano Angelaen_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Physiological Sciences.en_ZA
dc.date.accessioned2023-03-07T10:32:31Z
dc.date.accessioned2023-05-18T07:08:29Z
dc.date.available2023-03-07T10:32:31Z
dc.date.available2023-05-18T07:08:29Z
dc.date.issued2023-03
dc.descriptionThesis (MSc)--Stellenbosch University, 2023. en_ZA
dc.description.abstractENGLISH 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.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: lnleiding: Estrogeen- en estrogeenreseptor-ge·nduseerde seinoordrag speel 'n belangrike rol in borskanker ontwikkeling en bevordering. Studies het getoon dat sekere menopousale hormoonterapiee (MHT's) wat estrogeen en estrogeen in kombinasie met progestogene bevat, die risiko van indringende borskanker verhoog. Saamgestelde-bioidentiese hormoonterapiee (cBHTs), wat nie deur die FDA goedgekeur of gereguleer is deur die Medisynebeheerraad van Suid-Afrika nie, het 'n gewilde MHT geword, en word as veiliger doeltreffende alternatiewe geadverteer. Estrogeen alleen en in kombinasie met progestogene soos medroxyprogesteroon asetaat (MPA) en norethindrone (NET) verhoog bors sel proliferasie, migrasie en indringing. Dit is dus belangrik om die uitwerking van saamgestelde estrogeenformulerings in die ontwikkeling en vordering van borskanker te bepaal. Hierdie studie het ten doel om 'n vergelykende profiel te verskaf van die effekte van tradisionele menopousale terapiee, nl. (estrone + MPA en estrone + NETA), 'n FDA-goedgekeurde bioidentiese formulering (oestradiol + progesteroon (bE2+bP4)) met die van saamgestelde bioidentiese biest hormoonformulering E2 + estriol (bE2+bE3) op die vordering van borskanker. Metodes: Menslike ER+ borsadenokarsinoomselle (MCF7) is gebruik. Proliferasie is geassesseer deur die sellewensvatbaarheid deur wateroplosbare tetrazolium sout (WST-1) toetse te bepaal. Die selsiklus is met vloeisitometrie geanaliseer. Westelike klad ontledings is uitgevoer om die proliferasiemerker MCM2, die Pl3K/Akt seinweg en epiteel-na-mesenkiemale oorgangsmerkers (EMT) te assesseer; E-cadherin, N-cadherin, Slac en b-catenin. Migrasie is gemeet deur 'n wondgenesingstoets. Resultate en bespreking: Alle behandelingskombinasies het die lewensvatbaarheid van kankerselle aansienlik verhoog. Die selsiklus analise toon dat FDA-goedgekeurde estrone + MPA en estrone + NETA behandelings die ophoping van MCF7 selle in die GO/G1 fase van die selsiklus ge·nduseer het. Westelike klad-analise het aan die lig gebring dat alle hormoonbehandelings nie die Pl3K/Akt- weg geaktiveer het nie. Verder het behandeling van BE2 + BP4 mesenkiemale kenmerke van EMT aangedui. Die wondgenesingstoets het getoon dat die hormoonbehandelings nie migrasie veroorsaak het nie. Gevolgtrekkings: Volgens ons bevindinge is daar beide ooreenkomste en verskille tussen die saamgestelde biest- kombinasies en FDA-goedgekeurde hormoonformulerings. Wat betref, cBHT, verhoog die lewensvatbaarheid van selle op 'n wyse wat ooreenstem met die FDA-goedgekeurde formulerings. Soortgelyk aan FDA-goedgekeurde terapiee, het hulle nie migrasie veroorsaak of die Akt-weg vir selproliferasie geaktiveer nie. In teenstelling met hul FDA-goedgekeurde ewekniee, het cBHT-formulerings verskillende effekte op EMT en die selsiklus getoon. Saam demonstreer hierdie resultate dat cBHT-behandelings nie die wee gestimuleer het wat verband hou met borskankerprogressie wat deur die FDA-goedgekeurde formulerings gestimuleer is nie. Toekomstige aanbevelings sluit in die ondersoek na die uitwerking van cBHT- preparate op ander wee wat betrokke is by borskankerinisiasie en -bevordering ondersoek in vergelyking met die FDA-goedgekeurde formulerings.af_ZA
dc.description.versionMastersen_ZA
dc.format.extentxix, 91 pages : illustrations (some color)en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/127181
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch Universityen_ZA
dc.rights.holderStellenbosch Universityen_ZA
dc.subject.lcshBreast -- Cancer -- Treatmenten_ZA
dc.subject.lcshMenopause -- Hormone therapyen_ZA
dc.subject.lcshMenopausal hormone therapies (MHTs)en_ZA
dc.subject.lcshFood and drug administrationen_ZA
dc.subject.lcshEstrogen -- Therapeutic useen_ZA
dc.subject.lcshHuman ER+ mammary adenocarc noma cellsen_ZA
dc.subject.lcshHormone therapy -- Methodsen_ZA
dc.subject.nameUCTDen_ZA
dc.titleA comparison of compounded-bioidentical hormone formulations versus FDA-approved hormone formulations in breast cancer progressionen_ZA
dc.typeThesisen_ZA
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Masters Degrees (Physiological Sciences)