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Investigating the effect of chemotherapeutic agents, Doxorubicin and Paclitaxel, in combination with Dodonaea viscosa on breast cancer
Thesis (PhD)--Stellenbosch University, 2025.
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Stellenbosch : Stellenbosch University
2026
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| _version_ | 1867613784233738240 |
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| access_status_str | Open Access |
| author | Van Eck, Janke |
| author2 | Engelbrecht, Anna-Mart |
| author_browse | Engelbrecht, Anna-Mart Van Eck, Janke |
| author_facet | Engelbrecht, Anna-Mart Van Eck, Janke |
| author_sort | Van Eck, Janke |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2025. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/134846 |
| institution | Stellenbosch University (South Africa) |
| last_indexed | 2026-06-10T12:41:38.867Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/134846 Investigating the effect of chemotherapeutic agents, Doxorubicin and Paclitaxel, in combination with Dodonaea viscosa on breast cancer Van Eck, Janke Engelbrecht, Anna-Mart Kaschula, Catherine H. Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Breast -- Cancer -- Chemotherapy Dodonaea -- Therapeutic use Drug resistance in cancer cells -- Treatment Chemotherapy, Combination Medicinal plants -- Therapeutic use Doxorubicin -- Mechanism of action Paclitaxel -- Mechanism of action Mice -- Tumors Apoptosis -- Animal models UCTD Thesis (PhD)--Stellenbosch University, 2025. Van Eck, J. 2025. Investigating the effect of chemotherapeutic agents, Doxorubicin and Paclitaxel, in combination with Dodonaea viscosa on breast cancer. Unpublished doctoral dissertation. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/21fc164b-3d7e-422e-9cef-f58c24929223 ENGLISH ABSTRACT: Introduction: Breast cancer remains a major global health challenge, particularly among women. While chemotherapeutic agents such as doxorubicin (DXR) and paclitaxel (PTX) are widely used, their effectiveness is limited by off-target effects, systemic toxicity, and acquired resistance. This highlights the need for therapies that selectively target cancer cells while sparing healthy tissue. Phytotherapy offers a promising alternative, with plant extracts like Dodonaea viscosa demonstrating notable anticancer potential. However, its interaction with DXR or PTX in breast cancer has not been explored. To address this gap, this study examined the combined effects of D. viscosa with DXR or PTX on key cancer-related pathways, including proliferation, migration, and apoptosis. Materials & Methods: Breast cancer cell lines (MDA-MB-231, MCF7) and non-malignant breast epithelial cells (MCF12A) were treated with D. viscosa, DXR, PTX, or their combinations. Cell viability was assessed using an MTT assay, and IC₅₀ values were calculated to determine treatment potency and selectivity indices. Synergism and optimal dose combinations were evaluated via isobologram analysis. Cell migration was measured using wound healing assays, while clonogenic assays assessed long-term proliferative capacity. Western blotting examined markers of proliferation, epithelial-mesenchymal transition (EMT), DNA damage, and apoptosis. In vivo, female mice bearing E0771 tumours received D. viscosa (300 mg/kg), DXR (5 mg/kg), PTX (30 mg/kg), or combinations. After the treatment period, mice were euthanised, blood was collected, and tumours were harvested for burden assessment, histopathology, and molecular analysis of proliferation, EMT, DNA damage, and apoptosis. Results: Combination treatments enhanced anticancer efficacy compared to single agents, while remaining non-toxic to normal breast epithelial cells. In vitro, the combinations most effectively reduced cell migration and clonogenic survival. Western blotting confirmed synergistic activity, with increased epithelial markers, reduced mesenchymal markers, and elevated DNA damage and apoptotic proteins. In vivo, combined treatment reduced tumour volume and growth rate, suppressed EMT, enhanced apoptosis, and lowered Ki-67 expression. Conclusion: This study provides the first evidence that D. viscosa potentiates the efficacy of DXR and PTX in breast cancer by targeting key processes such as proliferation, migration, and apoptosis. These findings support further exploration of D. viscosa and other combination-based strategies to improve treatment efficacy, optimise dosing, and enhance patient outcomes and quality of life. AFRIKAANSE OPSOMMING: Inleiding: Borskanker bly steeds ’n beduidende wêreldwye gesondheidsuitdaging. Chemoterapeutiese middels soos doxorubisien (DXR) en paclitaxel (PTX) word algemeen in behandeling gebruik, maar hul kliniese bruikbaarheid word egter beperk deur sistemiese toksisiteite, nie-teikeneffekte en ontwikkeling van terapeutiese weerstand. Daar bestaan dus ’n dringende behoefte aan terapeutiese strategieë wat kankerselle selektief teiken terwyl skade aan gesonde weefsel tot die minimum beperk word. Fitoterapie het na vore getree as ’n belowende en volhoubare alternatief met die potensiaal om veiliger kankerbehandelings te bied. Hierdie veld het beduidende belangstelling getrek met natuurlike plant-ekstrakte soos Dodonaea viscosa, wat belowende anti-kanker- en sitotoksiese eienskappe toon. Alhoewel dit veelbelowend is, bly die interaksie daarvan met DXR of PTX in die konteks van borskanker onbekend. Hierdie studie het hierdie gaping aangespreek deur die gekombineerde effekte van Dodonaea viscosa en DXR of PTX op kritieke meganismes onderliggend aan kankerprogressie, insluitend proliferasie, migrasie en apoptose, te ondersoek. Metodes: Borskanker-sellyne (MDA-MB-231 en MCF7) en nie-maligne bors-epiteelselle (MCF12A) is blootgestel aan óf D. viscosa, DXR, PTX, óf ’n D. viscosa-chemoterapie kombinasie. Sellewensvatbaarheid is geëvalueer met ’n MTT-toets, en IC₅₀-waardes is bereken om die selektiwiteitsindeks van elke behandeling te bepaal. ‘n Isobologram-analise is vervolgens uitgevoer om moontlike sinergisme tussen D. viscosa en DXR of PTX te evalueer, asook om die mees effektiewe konsentrasiekombinasies te identifiseer. ’n Wondsgenesingstoets is gebruik om selmigrasie te evalueer, terwyl ’n klonogeniese oorlewingsanalise die vermoë van selle om kolonies te vorm, ontleed het. Om bevindings te versterk, is Western blot-analise gebruik om proteïenuitdrukking van sleutelaanduiders in selproliferasie, epiteel-tot-mesenchiemale-oorgang (EMT), DNA-beskadiging en apoptotiese seldood te bepaal. In vivo is wyfie-muise geïnokuleer met E0771-borskankerselle om ’n tumor-draende model te vestig. Muise is behandel met óf D. viscosa (300 mg/kg), DXR (5 mg/kg), PTX (30 mg/kg), óf ’n kombinasie daarvan. Na die behandelingsperiode is die muise ge-euthaniseerer, bloed versamel en tumore verwyder. Tumore is onderwerp aan tumorvolume bepalings en histopatologiese analise. Verder is molekulêre toetse gedoen deur selproliferasie-, EMT-, DNA-beskadiging- en apoptose in tumorweefsel te evalueer. Resultate: Kombinasieterapie het verbeterde anti-kanker- en sitotoksiese effekte getoon in vergelyking met enkelbehandelings, terwyl dit nie-toksies was teenoor normale bors-epiteelselle. In vitro het kombinasiegroepe die grootste vermindering in selmigrasie en klonogeniese oorlewingspotensiaal getoon. Western blot-resultate het sinergisme bevestig, soos blyk uit die opregulering van epiteelmerkers, afregulering van mesenchiemmerkers en verhoogde uitdrukking van DNA-beskadigings- en apoptosemerkers. Verder het muise wat aan gekombineerde behandelings blootgestel is, ’n afname in beide tumorgrootte en tumorgroei-tempo getoon. Hierdie tumore het verminderde EMT-aktiwiteit en ’n verhoogde apoptotiese respons vertoon. Histologiese ontleding het ook ’n vermindering in die Ki-67-indeks aangetoon. Gevolgtrekking: Hierdie studie lewer die eerste bewys dat D. viscosa die terapeutise effekte van DXR en PTX in borskanker kan versterk deur die kritieke kankerverwante prosesse te teiken, insluitend selproliferasie, migrasie en apoptose. Hierdie bevindinge bied oortuigende ondersteuning vir verdere ondersoek na D. viscosa en ander nuwe kombinasie-gebaseerde terapeutiese strategieë, wat die potensiaal het om behandelingsdoeltreffendheid te verbeter, dosisregimes te optimaliseer, en uiteindelik pasiëntuitkomste en lewenskwaliteit te bevorder. Doctoral 2026-01-12T12:19:34Z 2026-01-12T12:19:34Z 2025-12 Thesis https://scholar.sun.ac.za/handle/10019.1/134846 Stellenbosch University xxiii, 172 pages : illustrations, maps application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Breast -- Cancer -- Chemotherapy Dodonaea -- Therapeutic use Drug resistance in cancer cells -- Treatment Chemotherapy, Combination Medicinal plants -- Therapeutic use Doxorubicin -- Mechanism of action Paclitaxel -- Mechanism of action Mice -- Tumors Apoptosis -- Animal models UCTD Van Eck, Janke Investigating the effect of chemotherapeutic agents, Doxorubicin and Paclitaxel, in combination with Dodonaea viscosa on breast cancer |
| title | Investigating the effect of chemotherapeutic agents, Doxorubicin and Paclitaxel, in combination with Dodonaea viscosa on breast cancer |
| title_full | Investigating the effect of chemotherapeutic agents, Doxorubicin and Paclitaxel, in combination with Dodonaea viscosa on breast cancer |
| title_fullStr | Investigating the effect of chemotherapeutic agents, Doxorubicin and Paclitaxel, in combination with Dodonaea viscosa on breast cancer |
| title_full_unstemmed | Investigating the effect of chemotherapeutic agents, Doxorubicin and Paclitaxel, in combination with Dodonaea viscosa on breast cancer |
| title_short | Investigating the effect of chemotherapeutic agents, Doxorubicin and Paclitaxel, in combination with Dodonaea viscosa on breast cancer |
| title_sort | investigating the effect of chemotherapeutic agents doxorubicin and paclitaxel in combination with dodonaea viscosa on breast cancer |
| topic | Breast -- Cancer -- Chemotherapy Dodonaea -- Therapeutic use Drug resistance in cancer cells -- Treatment Chemotherapy, Combination Medicinal plants -- Therapeutic use Doxorubicin -- Mechanism of action Paclitaxel -- Mechanism of action Mice -- Tumors Apoptosis -- Animal models UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/134846 |
| work_keys_str_mv | AT vaneckjanke investigatingtheeffectofchemotherapeuticagentsdoxorubicinandpaclitaxelincombinationwithdodonaeaviscosaonbreastcancer |