Browsing by Author "Almnayan, Danah"
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Item Characterization of VR118 quinacrine derivative as a potential anticancer agent(Laurentian University of Sudbury, 2014-03-17) Almnayan, DanahThe discovery and development of effective chemotherapeutic agents in the past few decades have immensely enhanced the treatment and management of human cancer. However, because these drugs are associated with adverse side effects, high genotoxicity, risk for secondary cancers and devastating effects on the patients’ immune system; the need for developing more effective anticancer agents remains. A priority Research shows that 9-aminoacridine (9AA) derivatives have substantial anticancer properties. The pharmacological properties of this agent are well characterized and this scaffold has been widely used to treat different diseases for decades. Quinacrine is a 9AA derivative, which was first discovered as an antimalarial compound in 1930’s and since then had been widely used in treating a variety of parasitic infections and demonstrated potential for cancer treatment. Importantly, the polypharmacology of Quinacrine makes it an attractive drug to treat a variety of cancers. Quinacrine acts by specifically targeting cellular signaling pathways that play an important role in cell survival. Given the distinctive cancer treating abilities of Quinacrine by specifically targeting cellular signaling pathways, it was the objective of this study to develop a compound that has similar properties as Quinacrine but has better efficacy and selectivity in targeting tumor cells. Therefore, for this project we created derivatives of 9AA compound using hybrid pharmapore approach and examined one of the derivatives of Quinacrine compound named VR118. After performing a series of experiments to test the efficacy and selectivity of the Quinacrine derivative VR118, I came to the conclusion that VR118 is highly effective in treating cancer cells and have the potential to selectively target cancer cells without causing severe harm to normal cells at concentrations applicable for malignant cell lines. This report discusses the efficacy and selectivity of VR118 compound in targeting cellular signaling pathways and the mechanisms through which VR118 kills cancer cells.Item Immune - modulatory effects of sidr honey: implications for anti-proliferative effects on cancer cells(2020-10-23) Almnayan, DanahHoney has become popular as a potential treatment for several ailments, including many cancers. Being a natural product, honey is often considered to be a safe and inexpensive adjunct or sometimes even an alternative to the currently available cancer treatments (including chemotherapy and radiotherapy) that have adverse side effects. Honeys from different parts of the world have shown anti-proliferative, immune-modulatory, and anti-inflammatory actions. Yemeni Sidr Honey (YSH) is a world-renowned honey whose anti-inflammatory activity suggests the possibility of underlying anti-cancer and/or immune-modulatory actions. Our studies have shown that treatment with 1% YSH is able to inhibit proliferation, and induce apoptosis in breast cancer cell lines (MDA-MB-231 and MCF-7) and cervical cancer cell lines (Hela). We also showed that THP-1 monocyte-like cells differentiated by treatment with phorbol ester and then treated with YSH affected their polarization into M1 or M2 macrophages: treatment with YSH for 24 h, enhanced the expression of the M1 phenotype while treatment of the macrophages with LPS and YSH for 48 h increased the level of M2 markers of differentiation. Further, co-culture of the M1 differentiated macrophages with breast cancer cells showed that treatment of the macrophages with YSH decreased tumour cell growth and increased apoptosis. These results suggest treatment with YSH is able to impact cancer via two separate mechanisms: direct impacts on cancer cell survival and activation of anti-tumour immune system (monocyte) activation.