رسالة جامعية
In vitro effect of a sirtuin inhibitor and its possible synergistic effect with a potential tubulin inhibitor on breast cancer cell lines
| العنوان: | In vitro effect of a sirtuin inhibitor and its possible synergistic effect with a potential tubulin inhibitor on breast cancer cell lines |
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| المساهمون: | Mhlanga, Thandi, Selepe, Mamoalosi A., Joubert, Annie M., Mahlangu, Sandisiwe |
| بيانات النشر: | University of Pretoria |
| سنة النشر: | 2023 |
| المجموعة: | University of Pretoria: UPSpace |
| مصطلحات موضوعية: | Tubulin inhibitor, Sirtuin inhibitor, Breast cancer, cancer, Chemotheraoutics, Isoflavone, Benzofuran, UCTD |
| الوصف: | Dissertation (MSc (Human Physiology))--University of Pretoria, 2022. ; Introduction Breast cancer is among the most prevalent cancers, constituting 11.7% of global incidences and 14.32% of new diagnoses in South Africa in 2020. Owing to the high prevalence of breast cancer, there is an increasing need for anti-cancer drugs with high efficacy and minimal or no side effects. The process of drug design is integral for producing drugs that meet these needs. This is achieved by developing drugs targeting specific pathways known to be involved in the development of cancers. One of the most promising avenues in cancer drug development—currently used in clinical treatment of cancer—is combination therapy, that allows for improved efficacy through simultaneous targeting of different pathways such that the net effect exceeds that of the individual drugs. In this study the in vitro effects of a newly synthesised sirtuin inhibitor 6-methoxy-4',6'-dimethylisoflavone-2',5'-quinone (PK108-C3) and a potential tubulin inhibitor 5-hydroxy-3-(2',3',4'-trimethoxybenzoyl)-4,7-dimethylbenzo[b]furan (PK-92) were investigated individually and in combination. The benzofuran and isoflavone derivatives were assessed for the ability to reduce proliferation through cell death induction. Methods The effects of PK-92 and PK108-C3 on cell proliferation and metabolic activity were evaluated spectrophotometrically using crystal violet staining and dimethylthiazolyl-diphenyl-tetrazolium bromide assays in both the Monroe Dunaway Anderson Foundation Metastatic Breast Cancer 231 (MDA-MB-231) and Michigan Cancer Foundation-7 (MCF-7) cell lines. Morphological changes were investigated using light microscopy (haematoxylin and eosin staining) and polarisation-optical transmitted light differential interference contrast (PlasDIC) microscopy. Cell cycle progression, possible induction of apoptosis (annexin V- fluorescein isothiocyanate (FITC)) and mitochondrial membrane potential (MMP) disruption were investigated using flow cytometry. Spectrophotometry ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | A2023; https://repository.up.ac.za/handle/2263/89699Test |
| DOI: | 10.25403/UPresearchdata.22120355 |
| الإتاحة: | https://doi.org/10.25403/UPresearchdata.22120355Test https://repository.up.ac.za/handle/2263/89699Test |
| حقوق: | © 2022 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| رقم الانضمام: | edsbas.1E793852 |
| قاعدة البيانات: | BASE |
| DOI: | 10.25403/UPresearchdata.22120355 |
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