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

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.

Grantor dc:publisher.institution

University of Bradford

Author dc:creator

• Masood, Ayesha

Advisors dc:contributor.advisor

• Najafzadeh, Mojgan
• Kauser, Sobia

• Malignant melanoma
• Retinol
• Umbilical Cord Blood Stem Cell-Derived Exosomes
• Skin cancer
• Comet assay
• Western blotting
• RT–qPCR
• CCK8 assay
• Anti-cancer

Statement dc:rights

• <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.

Language dc:language.iso

en

Repository record dc:identifier.uri

https://bradscholars.brad.ac.uk/handle/10454/20888

OAI identifier oai:identifier

oai:bradscholars.brad.ac.uk:10454/20888