Antitumor activity of Urtica dioica seed extract on diethylnitrosamine-induced liver carcinogenesis in rats

Hepatocellular carcinoma (HCC) is a significant health problem for human life; therefore, new therapeutic approaches are essential. In vitro studies have shown that the extract of Urtica dioica seed extract (UDSE) may be a crucial protective agent to prevent HCC. Therefore, this study aimed to investigate the antitumor efficacy of UDSE in the process of carcinogenesis induced by diethylnitrosamine (DENA). The antitumor efficacy was evaluated by examining liver tissue histopathology and expression of Hep par-1, alpha-fetoprotein (AFP), caspase-3, and inducible nitric oxide synthase (iNOS) in the liver tissue and activities/levels of aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), carbohydrate antigen (CA) 15-3, CA 19-9, CA 125-II in the serum, and also total oxidative stress (TOS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant status (TAS) in the serum and liver. In addition, real-time PCR was used to evaluate the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-1 beta, IL-6), and proliferating cell nuclear antigen (PCNA) in liver tissue. It was observed that DENA application increased liver function tests, cancer markers, apoptosis, and proinflammatory cytokine levels, but UDSE application and DENA suppressed these increases. The findings and histopathological data demonstrated that the UDSE has a very significant antitumor efficacy on the process of DENA-induced hepatocellular carcinogenesis, which appears to be attributable to its antioxidant, anti-apoptotic, and anti-proliferative activity.