Alloimperatorin attenuates lung tumor progression by targeting oxidative stress and nuclear kappa B factor/Nrf2 pathway dysregulation

Abstract: BACKGROUND: Diethylnitrosamine (DEN) is a potent environmental carcinogen commonly found in cigarette smoke and polluted air, which is strongly associated with the initiation and progression of lung cancer through oxidative stress, inflammation, and dysregulated cell signaling. Alloimperatorin, a bioactive furanocoumarin compound isolated from Angelica dahurica , has demonstrated anti-inflammatory, antioxidant, and anticancer potential. The current study was designed to explore the chemoprotective effect of alloimperatorin against DEN-induced lung cancer in rats and explore the underlying signaling pathways. MATERIALS AND METHODS: Lung carcinogenesis was induced in male Wistar rats via intraperitoneal administration of DEN, and rats received the oral administration of alloimperatorin for 8 weeks. The lung function, body weight, tumor markers, phase I, phase II, polyamine, inflammatory parameters, inflammatory cytokines, and antioxidant enzymes were assessed. Quantitative histopathological analysis and histopathological observation were done in the lung tissue. RESULTS: Alloimperatorin significantly ameliorated the tumor burden, tumor number, mean tumor size, and improved histological architecture. Alloimperatorin ameliorate the level of tumor markers (5’-nucleotidase, aryl hydrocarbon hydroxylase, adenosine deaminase, lactate dehydrogenase, Hexosamine, Hexose), hematological parameters (total leucocytes, lymphocytes, total white blood cells count, neutrophils, monocytes, red blood cells counts), pro-inflammatory cytokines (tumor necrosis factor-alpha, L-1β, interleukin 4 [IL-4], IL-6, IL-10, IL-18), inflammatory parameters (cyclooxygenase-2, PGE 2 , vascular endothelial growth factor, nuclear kappa B factor [NF-κB]), apoptosis (Bax, Bcl-2, caspase-3) while restoring antioxidant enzyme (superoxide dismutase, catalase, glutathione (GSH) peroxidase, GSH, malonaldehyde) activities. In addition, it enhanced the level of HO-1 and Nrf 2 . CONCLUSION: Alloimperatorin ameliorate the lung cancer via alteration of the NF-κB and Nrf 2 signalling pathway.