Drug Design, Development and Therapy (Dec 2018)
Gamma linolic acid regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DEN induced Hepatocellular carcinoma
Abstract
Hong Cui,1 Feng Han,1 Ling Zhang,1 Li Wang,1 Mukesh Kumar2 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450008, China; 2Chandra Shekhar Singh College of Pharmacy, Allahabad, India Introduction: Hepatocellular carcinoma (HCC) is one of the known major health problems across the globe, and is sixth ranked among all cancer, due to its high mortality rate. Polyunsaturated fatty acids (PUFAs) play an important role in the formation of a cell membrane, along with the fluidity of the membrane and proteins. Gamma linolenic acid (GLA) is member of the ω-6 family of PUFAs and converts into the arachidonic acid via a series of elongation and desaturation reactions. The aim of the current investigation was to scrutinize the effect of GLA on mitochondrial mediated apoptosis and anti-inflammatory pathway against diethylnitrosamine (DEN) induced HCC.Materials and methods: Chemical carcinogenesis in Wistar rats was introduced by an intraperitoneal dose of DEN (200 mg/kg). The rats received the various doses of GLA for 22 weeks. The progressions of serum biomarkers and histopathology components of hepatic tissue were used to access the prophylactic effects. The antioxidant parameters, cancer preventive agent status, and apoptosis mechanism were reviewed to scrutinize the possible mechanism.Results: Dose-dependent treatment of GLA significantly (P<-0.001) modulated the hepatic nodules, hepatic, body weight, antioxidant, and non-hepatic parameters. Curiously, the Real-time polymerase chain reaction (RT-PCR) and immunoblotting showed the GLA altered reduced the hypoxic microenvironment, mitochondrial mediated death apoptosis, and anti-inflammsatory pathways.Conclusion: On the basis of the above results, we can conclude that the GLA exhibited a chemoprotective effect against DEN induced HCC that might be due to the altered hypoxic microenvironment, mitochondrial mediated death apoptosis, and anti-inflammatory pathway, respectively. Keywords: gamma linolenic acid, apoptosis, hepatocellular carcinoma, diethynitrosamine, gene expression
