An in vitro assessment of pharmacodynamic interactions between selected herbal extracts and anticancer chemotherapeutic agents
- Hwehwe, Nyashadzashe, Swanepoel, Bresler
- Authors: Hwehwe, Nyashadzashe , Swanepoel, Bresler
- Date: 2024-04
- Subjects: Chemotherapy , Herbs -- Therapeutic use , Antineoplastic agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/63506 , 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. , Thesis (MPharm) -- Faculty of Health Sciences, School of Clinical Care & Medicinal Sciences, 2024
- Full Text:
- Date Issued: 2024-04
- Authors: Hwehwe, Nyashadzashe , Swanepoel, Bresler
- Date: 2024-04
- Subjects: Chemotherapy , Herbs -- Therapeutic use , Antineoplastic agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/63506 , 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. , Thesis (MPharm) -- Faculty of Health Sciences, School of Clinical Care & Medicinal Sciences, 2024
- Full Text:
- Date Issued: 2024-04
Mathematical modelling of the tumour treatment with chemotherapy
- Authors: Nyaweni, Fundile Sindy
- Date: 2024-04
- Subjects: Mathematical models , Mathematics , Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/64289 , vital:73672
- Description: In this study, a cancer disease model incorporating predator-prey dynamics between immune cells and tumor cells, as well as competition between tumor cells and normal cells, is formulated in an attempt to understand the interaction dynamics that govern the complex interplay within the tumor microenvironment. Mathematical analysis is employed to derive conditions for the boundedness of solutions and to discuss disease thresholds such as the basic reproduction number, R0. Equilibrium points are identified, and stability conditions for the system are derived. Sensitivity analysis is used to assess uncertainties in the parameters of the model, specifically their impact on R0. Numerical simulations are conducted, utilizing the Runge-Kutta scheme to solve the model. Furthermore, optimal control (OC) techniques are applied to examine the role of chemotherapy in enhancing tumor cell elimination and minimizing adverse effects on immune cells and normal cells. The improved model, incorporating normal cells, anticancer drugs, and immune cells, allows for a more comprehensive analysis of the dynamic interactions within the biological system. The optimal control is determined using the forward-backward sweep numerical method. The numerical simulation is carried out in MATLAB to validate and complement the analytical findings. The results indicate that a low concentration of the drug leads to a prolonged period for tumor clearance. Conversely, a higher drug concentration results in quicker tumor clearance, albeit with adverse effects on normal and effector cells. The OC identifies when to stop the treatment once the tumor clears. Furthermore, OC facilitates the regeneration of normal and immune cells beyond treatment, in contrast to a control scenario without optimization. The findings highlight the importance of early detection and careful chemotherapy dosage selection for effective and personalized cancer treatment strategies. , Thesis (MSc) -- Faculty of Science, School Computer Science, Mathematics, Physics and Statistics, 2024
- Full Text:
- Date Issued: 2024-04
- Authors: Nyaweni, Fundile Sindy
- Date: 2024-04
- Subjects: Mathematical models , Mathematics , Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/64289 , vital:73672
- Description: In this study, a cancer disease model incorporating predator-prey dynamics between immune cells and tumor cells, as well as competition between tumor cells and normal cells, is formulated in an attempt to understand the interaction dynamics that govern the complex interplay within the tumor microenvironment. Mathematical analysis is employed to derive conditions for the boundedness of solutions and to discuss disease thresholds such as the basic reproduction number, R0. Equilibrium points are identified, and stability conditions for the system are derived. Sensitivity analysis is used to assess uncertainties in the parameters of the model, specifically their impact on R0. Numerical simulations are conducted, utilizing the Runge-Kutta scheme to solve the model. Furthermore, optimal control (OC) techniques are applied to examine the role of chemotherapy in enhancing tumor cell elimination and minimizing adverse effects on immune cells and normal cells. The improved model, incorporating normal cells, anticancer drugs, and immune cells, allows for a more comprehensive analysis of the dynamic interactions within the biological system. The optimal control is determined using the forward-backward sweep numerical method. The numerical simulation is carried out in MATLAB to validate and complement the analytical findings. The results indicate that a low concentration of the drug leads to a prolonged period for tumor clearance. Conversely, a higher drug concentration results in quicker tumor clearance, albeit with adverse effects on normal and effector cells. The OC identifies when to stop the treatment once the tumor clears. Furthermore, OC facilitates the regeneration of normal and immune cells beyond treatment, in contrast to a control scenario without optimization. The findings highlight the importance of early detection and careful chemotherapy dosage selection for effective and personalized cancer treatment strategies. , Thesis (MSc) -- Faculty of Science, School Computer Science, Mathematics, Physics and Statistics, 2024
- Full Text:
- Date Issued: 2024-04
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