- Title
- An in vitro assessment of pharmacodynamic interactions between selected herbal extracts and anticancer chemotherapeutic agents
- Creator
- Hwehwe, Nyashadzashe
- Creator
- Swanepoel, Bresler
- Subject
- Chemotherapy
- Subject
- Herbs -- Therapeutic use
- Subject
- Antineoplastic agents
- Date Issued
- 2024-04
- Date
- 2024-04
- Type
- Master's theses
- Type
- text
- Identifier
- http://hdl.handle.net/10948/63506
- Identifier
- vital:73383
- Description
- Cancer is a disease caused by uncontrolled growth and spreading of abnormal cells to distant body parts. Approximately 19.3 million and 10 million new cancer cases and cancer deaths, respectively were recorded in 2020. Despite advancements in prevention and therapeutic strategies, cancer remains a global health problem. Cancer patients are increasingly seeking complementary and alternative medicines, of which herbal medicines are the most common form of CAM used by patients. Numerous in vitro and in vivo studies of herbal medicines in cancer have shown that they have antioxidant and anticancer (antitumor and anti-proliferative) properties. While concurrent use with conventional cancer treatments may improve treatment efficacy, alleviate chemotherapy-related side effects, boost the immune system, or impede drug resistance, it can also prompt drug-herbal interactions, and this may affect the pharmacodynamics and pharmacokinetics of the chemotherapeutic drug. This study aimed to determine relevant pharmacodynamic interactions with chemotherapeutic drugs and investigate such interactions' mechanisms. The objectives of the study were to screen the cytotoxicity effects of drug compounds, herbal extracts, and drug-herb combinations, to determine the ability of treatments to induce apoptosis, and to determine the most beneficial treatment. The cytotoxic effects of cisplatin in HeLa cells, tamoxifen in MCF7 cells, 5-fluorouracil in Caco-2 cells, and grapeseed, green tea, fermented rooibos, and green rooibos in all the listed cell lines were evaluated individually and in combination using the bis-Benzamide H 33342 trihydrochloride/propidium iodide (Hoechst 33342/PI) dual staining method. CompuSyn 1.0 Software was used to quantify synergism and antagonism. The mechanism of apoptosis induction of the different synergetic combinations, drug compounds, and herbal extracts was illustrated by quantitative fluorescence image analysis, specifically cell cycle analysis, phosphatidylserine translocation, mitochondrial membrane potential analysis, caspase 3 activation, and reactive oxygen species production using the relevant contrast dyes. Grapeseed displayed cytotoxicity towards MCF7 and HeLa cells (IC50 57.98 and 83.28 μg/mL, respectively). Green tea was only cytotoxic against HeLa cells at an IC50 of 91,92 μg/mL. None of the extracts displayed cytotoxicity against Caco-2 cells (IC50 values > 200μg/mL). If the herbal extracts had inconclusive IC50 values in the three cell lines subsequent experiments were conducted using 100 μg/mL. The results showed that most of the combinations were antagonistic but, some combinations had synergistic or enhancement effects(1:3 for cisplatin with grape seed or green tea and tamoxifen with grapeseed or green tea, and 3:1 for cisplatin with green tea as well as for tamoxifen with fermented rooibos or green rooibos, and all the 1:1 combinations of 5- fluorouracil with all herbal extracts) with a combination index (CI) < 1. Grape seed and green tea were found to induce apoptosis in the three cell lines. Assays that were conducted to detect apoptosis induction showed positive staining for phosphatidylserine (PS), activated caspase 3, and reactive oxygen species (ROS), mitochondrial membrane depolarization. Analysis of the cell cycle showed two things; 1) that grape seed and green tea were apoptotic in HeLa and MCF7 cells only, and 2) the extracts of green tea and green rooibos, and the combinations of grape seed with all drug compounds arrested the cell in more than one phase of the cell cycle. The combinations of grapeseed and green tea potentially induced apoptosis in various manners but those with both rooibos extracts were unclear in all the cell lines. The results for combinations with grapeseed and green tea are promising and provide a basis for further research as combinations of chemotherapeutic drugs and herbal extracts may be effective therapeutic strategies.
- Description
- Thesis (MPharm) -- Faculty of Health Sciences, School of Clinical Care & Medicinal Sciences, 2024
- Format
- computer
- Format
- online resource
- Format
- application/pdf
- Format
- 1 online resource (xxiii, 169 pages)
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Health Sciences
- Language
- English
- Rights
- Nelson Mandela University
- Rights
- All Rights Reserved
- Rights
- Open Access
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Hwehwe, N April 2024.pdf | 5 MB | Adobe Acrobat PDF | View Details Download |