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Evaluation of Anti-cancer effect of a Novel Formulation from Umbilical Cord Blood Stem CellDerived Exosomes and Retinoic acid as a potential therapeutic candidate against Malignant Melanoma
Masood, Ayesha
Masood, Ayesha
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End of Embargo
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The University of Bradford theses are licenced under a Creative Commons Licence.
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University of Bradford
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School of Chemistry & Biosciences. Faculty of Life Sciences
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2024
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PhD Thesis
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Abstract
This study focused on two potential therapeutic modalities with good safety profiles, i.e., Retinoic acid (RA) and Umbilical cord blood stem cell (CBSC)-derived exosomes as an anti-cancer drug. The current in vitro study has evaluated the genotoxicity and cytotoxicity of RA and CBSC-derived exosomes, either alone or combined, on lymphocytes from healthy individuals and melanoma patients and on the CHL-1 and FM55 melanoma cell lines. The optimal doses were identified as 10 µM for RA and 120 µl of 107 particles/ml for CBSC-derived exosomes. Both doses significantly exerted cytotoxic and genotoxic effects on FM55 and CHL-1 melanoma cells compared to lymphocytes from healthy and melanoma patients where both treatments showed genoprotective effect (***p<0.001) against oxidative stress induced by hydrogen peroxide (H2O2) and UVA+B (1.2mW/cm2).
Moreover, RA rescued DNA damage caused by oxidative stress in both healthy and melanoma lymphocytes. However, in both melanoma cell lines, RA aggravated the genotoxic effect (***p<0.001). Similar results were observed with the CBSC-derived exosomes treatment (***p<0.001). The combined treatment (10 µM RA + 120 µl of 107 particles/ml CBSC-derived exosomes) synergistically increased observed DNA damage in both melanoma cell lines. Moreover, the findings from Western blotting support the RT-qPCR results and the level of upregulation of Caspase-3, P53 and P21 was slightly higher using Western blotting compared to the RT-qPCR and significant initiation of apoptosis was evident in all treatment groups with downregulation of S100 and Bcl-2, particularly for the combined treatment of RA and CBSC-derived exosomes. Therefore, significant activation of p53-mediated apoptosis was detected in FM55 and CHL1 melanoma cells.
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Thesis
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PhD