Gamma linolic acid regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DEN induced Hepatocellular carcinoma

Abstract

IntroductionHepatocellular 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 methodsChemical carcinogenesis in Wistar rats was introduced by an intra-peritoneal 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.ResultsDose-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.ConclusionOn the basis of the above results, we can conclude that the GLA exhibited a chemo-protective effect against DEN induced HCC that might be due to the altered hypoxic microenvironment, mitochondrial mediated death apoptosis, and anti-inflammatory pathway, respectively.

Transcription Factors Linked to the Molecular Signatures in the Development of HCC on a Cirrhotic Background

“…The linoleic acid pathway regulates many physiological processes, then, its metabolic pathway is vital for metabolisms in cancer cells. According to the previous studies, defects in this pathway have been observed in HCC patients, therefore, our results con rm the previous ones [43,44]. Besides, pathways involved with chemical carcinogenesis and cell cycle are associated with cancer development.…”

Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model

“…For example, γ linolenic acid has been shown to reduce cell proliferation and promote the generation of ROS and apoptosis in HCC cell lines [25]. Furthermore, it had a chemo-protective effect against diethylnitrosamineinduced HCCs [26]. EPA-and DHA-enriched diet fed mice were shown to be metabolically healthier with lower lipid and fatty acid biosynthesis as well as upregulation of PPARα and lipid catabolism [27].…”

Gamma linolenic acid suppresses hypoxia-induced gastric cancer cell growth and epithelial-mesenchymal transition by inhibiting the Wnt/b-catenin signaling pathway

“…Despite the achievements in surgical resection and chemotherapy for the treatment of gastric cancer, its recurrence rate and metastasis rate are still high, and the median overall survival (OS) time of patients with metastatic disease is still very poor [3,4]. GLA is a promising bioactive molecule that has anticancer ac-tivity in many types of cancer [18,22,26,27], but its biological activity in gastric cancer is poorly understood. It has been reported that regular intake of GLA could reduce inflammation and inhibit the development of cancer [28][29][30].…”

“…In the past few decades, extensive studies have confirmed the potential anticancer effect of these fatty acids [18][19][20][21]. For examples, in vivo experiments have shown that GLA exhibits a dose-dependent regulatory effect on an experimental study on hepatocellular carcinoma [22]. Further studies of underlying molecular mechanisms indicated that GLA may exert a chemical protective effect on DEN-induced liver cancer by altering hypoxic microenvironment, mitochondria-mediated death, apoptosis, and anti-inflammatory pathways [22].…”

“…For examples, in vivo experiments have shown that GLA exhibits a dose-dependent regulatory effect on an experimental study on hepatocellular carcinoma [22]. Further studies of underlying molecular mechanisms indicated that GLA may exert a chemical protective effect on DEN-induced liver cancer by altering hypoxic microenvironment, mitochondria-mediated death, apoptosis, and anti-inflammatory pathways [22]. In addition, Chas et al used gas chromatography to establish a biochemical profile fatty acids (FA) in the adipose tissue and found that inflammatory breast cancer was associated with decreased levels of eicosapentaenoic acid (EPA) and GLA in breast cancer adipose tissue [23].…”