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Theses and dissertations (Applied Sciences)

Permanent URI for this collectionhttp://ir-dev.dut.ac.za/handle/10321/6

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Subject: search.filters.subject.Cancer cells

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    Active targeting of cancer cells using gemcitabine conjugated platinum nanoparticles
    (2017) Odayar, Kriya; Odhav, Bharti; Mohanlall, Viresh
    Nanotechnology is explained as the science of engineered materials and systems on a molecular scale. This innovation is currently used in a wide variety of applications which include using these nanoparticles as drug delivery vehicles. Such nanocarriers are relatively smaller than 100 nm in size with the ability to convey therapeutic drugs to a number of disease sites. Platinum-based nanoparticles have been extensively used in a number of applications namely catalysts, gas sensors, glucose sensors and cancer therapy. The properties of platinum nanoparticles (PtNP’s) typically depend on characteristics such as shape, particle size, elemental composition and structure, all of which can be manipulated and controlled in the fabrication process. Their unique size in the nanometer scale makes platinum nanoparticles an ideal candidate as targeted drug delivery vehicles. To target an anticancer drug to a diseased site is a distinctive feature of most studies, which aim to transfer an adequate dosage of the drug to cancer cells. Transport systems used as carriers of anticancer drugs offer numerous advantages, which include improved efficacy and a decrease in toxicity towards healthy cells when compared to standard drugs. The aim of this study was to determine the effect of platinum nanoparticles, gemcitabine and gemcitabine conjugated platinum nanoparticles (Hybrids) against cancer cells and healthy cells and to determine the mode of cell death and cell death pathways using flow cytometry. Platinum nanoparticles were synthesized via the reduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. Synthesized platinum nanoparticles and the hybrids were characterized by observing peaks at 301 nm and 379 nm respectively using UV-visible spectroscopy. TEM images revealed that the PtNP’s and the conjugate compounds were spherical in shape with core sizes of 1.14 nm - 1.65 nm and 1.53 - 2.66 nm respectively. The bioactivity platinum nanoparticles, gemcitabine and the hybrids were investigated using MCF7 and Melanoma cancer cells at different concentrations from 0.10 to 100 µg/ml. Results indicated that conjugated nanoparticles induced the highest cell inhibition against both cell lines compared to gemcitabine and platinum nanoparticles. Bioactivity against PBMC (peripheral blood mononuclear) cells indicated that all three compounds show little or no effect towards the healthy cell line compared to the control. Melanoma cell line was used to determine the mode of cell death. Apoptosis was detected using Annexin V-FITC to detect membrane changes, JC-1 to detect a loss in mitochondrial membrane potential and caspase-3 assay kits. Results indicated that a significant amount of cell death was caused by cleavage of caspase-3. Nanoparticle drug delivery is an area that has shown significant promise in cancer treatment. Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates. Imagine, something that is atleast or more than 80,000 times smaller than the edge of the ridge on a fingertip and unlocks a new wilderness into cancer research. Nanotechnology, known as the science of minute, is changing the approach to cancer and especially future diagnosis and treatment. Nanotechnology permits scientists to fabricate new apparatuses that are definitely smaller than cells, giving them the chance to attack tumor diseased cells. This innovation not just empowers practitioners to recognize malignancies prior but additionally holds the guarantee of halting cancer growth before it further develops. This progressive approach is so exact, specialists will in future be able to outline a unique treatment for an individual’s own restorative and hereditary profile. Researchers are designing nanoparticles that detect and destroy diseased cells and this optimistic innovation could be personalized for targeted drug delivery, enhanced imaging and ongoing affirmation of cancer cell death. The National Cancer Institute remains hopeful that facilitated development, nanotechnology will drastically change cancer treatment.
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    Modulating effects of Fumonisin B1 and Ochratoxin A on immune cells in human carcinoma
    (2005) Adam, Jamila Khatoon; Odhav, Bharti
    Fumonisin B1 (FB1) and ochratoxin A (OTA) represent examples of mycotoxins of greatest public health and agro-economic significance. They exert adverse effects on humans, animals and crops that result in illnesses and economic losses. Fumonisin B1 are cancerpromoting metabolites of Fusarium proliferatum and F verticillioides, (formerly moniliforme), and are implicated in oesophageal cancer. Ochratoxins are metabolites of both Aspergillus and Penicillium species. These compounds are known for their nephrotoxic effects in all animal species and may promote tumours in humans. In man OTA exhibits unusual toxicokinetics, with a half-life in blood of 840 h (35 days) after oral ingestion. Although much is known regarding the toxicology of these toxins, little is known of the effects of these toxins on the immune system. The aim of this study was to determine and compare the immunornodulating effects of FB1 and OTA in human carcinoma. Initial experiments involved isolating lymphocytes and neutrophils from healthy volunteers. The isolated cells were exposed to either FB1 or OTA on a dose and time dependent level and LD50 of the toxins was determined. Thereafter, challenge tests were performed, whereby lymphocytes and neutrophils isolated from volunteers, oesophageal cancer patients and breast cancer patients were exposed to the LD50 dose of either FB1 or OTA for the appropriate time. The effect of the toxins was demonstrated by viability studies, light microscopy and electron microscopy. Cytokine receptors (CK, TNF and CSF) were evaluated by immuno-cytochemical methods and the levels of circulating cytokines (IL -1, IL-6, IL-8, IL-10 and TNF-a) were determined using ELISA kits.
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    Anti-carcinogenic activity of Centella asiatica and Elytropappus rhinocerotis on a human colon cancer cell line
    (2012) Dwarka, Depika; Odhav, Bharti; Sewram, Vikash
    Recently our understanding of cancer has advanced in the realization that apoptosis and the genes that control it have a profound effect on the malignant phenotype. It is now clear that some oncogenic mutations disrupt apoptosis, leading to tumor initiation, progression or metastasis. Conversely, compelling evidence indicates that other oncogenic changes promote apoptosis, thereby producing selective pressure to override apoptosis during multistage carcinogenesis. Finally, it is now well documented that most cytotoxic anti-cancer agents induce apoptosis, raising the intriguing possibility that defects in apoptotic programs contribute to treatment failure. Because the same mutations that suppress apoptosis during tumor development also reduce treatment sensitivity, apoptosis provides a conceptual framework to link cancer genetics with cancer therapy. An intense research effort is uncovering the underlying mechanisms of apoptosis, such that, in the next decade, one envisions that this information will produce new strategies to exploit apoptosis for therapeutic benefit. Plants have a long history in cancer treatment. More than 3000 species have been known for their anti-cancer potential. Over 60% of currently used anti-cancer agents are derived in one way or another from higher plants. Indeed, compounds derived from natural sources, including plants, have played, and continue to play, a dominant role in the discovery of leads for the development of conventional drugs for the treatment of most human diseases especially cancer. Thus the aim of this study was to investigate if Centella asiatica and Elytropappus rhinocerotis possess anti-cancer potential and determine the effect on the modulation of apoptosis. In South Africa C. asiatica is known anecdotally to treat various forms of cancers and E. rhinocerotis is known to treat colic and diarrhoea. The anti-cancer activity of C. asiatica has been studied in some parts India but E. rhinocerotis has not been investigated. This study was conducted using polarity guided fractionation (aqueous, ethanolic, methanolic and hexane), thereafter these extracts were tested for their toxicity on a colon cancer cell line (CaCO-2) and on normal cells vi (PBMC). Subsequently, the most active extract was used to isolate the active fraction. The fraction that displayed toxicity on the CaCO-2 cells were further investigated for their ability to induce apoptosis by observing the morphological effects and DNA changes using acridine orange-ethidium bromide staining. Apoptosis was confirmed using Annexin V- PI staining. Nuclear effects were studied by DNA fragmentation and by agarose gel electrophoresis. Nuclear fragmentation was studied by flow cytometry using bromodeoxyuridine (BrDU). Pro-apoptotic changes were determined with Caspase III enzyme levels using flow cytometry. The results were compared to the effect of a known anti-carinogen - Taxol. The anti-oxidant activity was also evaluated for the different extracts. The ethanolic extracts of both C. asiatica and E. rhinocerotis showed more than 100% radical scavenging activity. The methanolic extract (125 μg/ml -500 μg/ml) showed cytotoxicity on the CaCO-2 cells and a proliferative effect on the PBMC. Apoptosis was confirmed in the methanolic extract for both plants and was therefore used to carry forth this study. This included early apoptotic changes observed by the morphological study i.e., membrane blebbing, nuclear condensation and the presence of apoptotic bodies, in both C. asiatica and E. rhinocerotis fractions demonstrated more non-viable apoptotic cells than the methanolic extracts. Late changes of apoptosis were also found as indicated by DNA laddering and a positive outcome with BrDU. Both the active fractions from C. asiatica and E. rhinocerotis showed more DNA laddering and active caspase III than the methanolic extract. These features indicate that C. asiatica and E. rhinocerotis cause apoptotic death of colon cancer cells CaC0-2. In conclusion, there was a significant increase in apoptosis of CaCO-2 cells with little alteration of PBMC in the presence of the methanolic extract of C. asiatica and E. rhinocerotis. The semipure fractions resulted in changes related to late apoptosis. The results suggest that C. asiatica and E. rhinocerotis induces apoptosis in CaCO-2 cells which is an important step in elucidating the underlying molecular mechanism for anti-tumour activity.