Saudi Cultural Missions Theses & Dissertations
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Item Restricted MODULATION OF HYPOXIA INDUCIBLE FACTOR 1 ALPHA PLAYS A KEY ROLE IN THE TREATMENT OF HEPATOCELLULAR CARCINOMA AND ACCELERATES WOUND HEALING IN DIABETIC PATIENTS(Cleveland State University, 2024-07-21) Alghamdi, Uthman; Zhou, AiminHypoxia Inducible Factor 1 (HIF-1) is a heterodimeric transcriptional factor that plays a physiological role in low oxygen concentration or hypoxia. HIF-1 consists of two dimers: HIF-1alpha (HIF-1α) and HIF-1beta (HIF-1β). HIF-1 is the active oxygen-sensing domain in the cytoplasm that leads to stabilizing and overexpression of HIF-1 in the cells during hypoxia. On the other hand, HIF-1β is a stable domain in the nucleus that is required to form a dimer with HIF-1α in the DNA to express the HIF-1 gene. Upregulation of HIF-1α by either hypoxia or drug molecules has been elucidated to overexpress more than 100 tumor genes. These genes are involved in developing angiogenesis (vascularization), metastasizing, cellular proliferation, switching to anaerobic metabolism, and cellular survival. Hepatocellular carcinoma (HCC) is one of the solid tumors that have a hypoxic intratumor environment and relies on overexpression of HIF-1α to overcome hypoxia and allow cancer cells to survive, proliferate, and metastasize in these harsh conditions. Targeting or downregulating the HIF-1α gene in HCC with chemical compounds may provide a treatment for this cancer. However, inducing and overexpression of HIF-1α has many of benefits, such as accelerating wound healing in diabetic patients. Diabetic patients suffer from hyperglycemia and thick blood that delay wound healing and may cause infections. Upregulation of HIF-1α expression in diabetic wounds will increase the speed of the repair process of wound healing. HIF-1α plays a crucial role in all phases of wound healing by facilitating cell division, growth factor secretion, cell migration, survival in hypoxic environments, and matrix synthesis. We screened the LOPAC drug library to discover several chemical compounds that either inhibit or stimulate HIF-1α expression. These drug candidates have been further investigated to confirm their activity against HIF-1α expression. These findings suggest that up or downregulation of HIF-1α expression by these drugs has played a key role in treating HCC and accelerating the wound healing process.19 0