Inhibition of nuclear factor kappa beta (NF-kβ) as therapeutic strategy for the treatment of IBD and cancer

  • Mohammed Khan

Student thesis: Doctoral Thesis

Abstract

Ulcerative colitis and colorectal cancer are progressively spreading in developed and developing countries. However, the current therapeutics does not provide complete cure to these conditions. It has been reported that inflammatory cytokines, overstimulated NF-kβ and overexpressed HIF-1α play pivotal role in inflammation and colorectal cancer. The traditional method of treatment offers not only detrimental effects on health due to non-selectivity but also burdens financially. Additionally, in a chronic condition of ulcerative colitis and colorectal cancer patients undergo bowel surgery which makes the life difficult to live. Therefore, there is pressing need to utilize natural therapeutic compounds to treat ulcerative colitis and colorectal cancer. These natural compounds possess potent inhibition potential against inflammatory cytokines, NF-kβ and HIF-1α. These compounds treat the inflammatory condition and colorectal cancer with minimum or no side effects as documented in clinical trials. However, these natural compounds have limited solubility in aqueous media due to which therapeutic potential of natural compounds are compromised. Therefore, nanotechnology can be employed to overcome the solubility issue of these natural compounds.

In the current work, we have formulated nanoparticles of low soluble natural antiinflammatory and anticancer agents such as curcumin, piceatannol and Caffeic acid phenethyl ester. Characterization and optimization have been performed to obtain suitable formation for the in vitro and in vivo experiment. Morphological studies were carried out by scanning electron microscopy. Significant increase in solubility has been confirmed in nanoparticles form. Cellular localization has been observed under phase contrast microscopy in MDA-MB-231, A549, HT-29 and CaCo-2 cells. Nanoparticles treated colon cancer cells has depicted the higher degree of v cytotoxicity, lower migration, less colony formation and decrease level of invasion than free drug in cancer cell lines. Nanoparticles treated cells have demonstrated low expression of inflammatory cytokines such as INF-γ, IL-6, IL-1β, TNF-α, and IL-10 in cancer cell lines. Stabilisation of nuclear proteins p65 and HIF-1α has been demonstrated significantly more in nanoparticles treated in lung cancer, breast cancer and colon cancer cell lines. The anti-inflammatory activity of these nanoparticles has been tested in mouse model of ulcerative colitis and it has been found that nanoparticles have higher therapeutic potential in inflammation than free drug.
Date of Award20 Jul 2018
Original languageEnglish
SponsorsVCRS
SupervisorMurtaza Tambuwala (Supervisor), Paul Mc Carron (Supervisor) & Paul Thompson (Supervisor)

Cite this

Inhibition of nuclear factor kappa beta (NF-kβ) as therapeutic strategy for the treatment of IBD and cancer
Khan, M. (Author). 20 Jul 2018

Student thesis: Doctoral Thesis