Gentiopicroside targets PAQR3 to activate PI3K/AKT signaling pathway and ameliorate glucose and lipid metabolism

AbstractDairy cows with fatty liver or ketosis display decreased insulin sensitivity and defects in the insulin receptor substrate (IRS)/PI3K/AKT signaling pathway. Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor and also a negative regulator of insulin signaling and peripheral insulin sensitivity. We investigated the hypothesis that PTEN may affect the insulin pathway-mediated hepatic glucose and lipid metabolism in dairy cows. Adenovirus vectors that over-express and silence PTEN were constructed, and then transfected into hepatocytes isolated from calves to investigate the effect of PTEN on PI3K/AKT signaling pathway. PTEN silencing increased the phosphorylation of AKT and the expression of PI3K but decreased the phosphorylation of IRS1, which increased the phosphorylation levels of glycogen synthase kinase-3β (GSK-3β) and expression of sterol regulatory element-binding protein-1c (SREBP-1c). Increased GSK-3β phosphorylation further up-regulated expression of the key enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6-Pase) involved in gluconeogenesis. Furthermore, the expression of SREBP-1c target gene fatty acid synthase (FAS) also increased significantly. We further showed that PTEN over-expression could reverse the above results. PTEN negatively regulates the enzymes involved in hepatic gluconeogenesis and lipid synthesis, which suggests that PTEN may be a therapeutic target for ketosis and fatty liver in dairy cows.

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Faculty Opinions recommendation of Rpn10 promotes tumor progression by regulating hypoxia-inducible factor 1 alpha through the PTEN/Akt signaling pathway in hepatocellular carcinoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734911165.793580826 ◽

2020 ◽

Author(s):

Leonardo Salmena

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Progression ◽

Signaling Pathway ◽

Hypoxia Inducible Factor ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Hypoxia Inducible Factor 1

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Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway

Journal of Chinese Integrative Medicine ◽

10.3736/jcim20110511 ◽

2011 ◽

Vol 9 (5) ◽

pp. 533-538 ◽

Cited By ~ 9

Author(s):

ZH Chu

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Phosphatidylinositol 3 Kinase ◽

Proliferation And Apoptosis ◽

Mcf 7 ◽

Phosphatidylinositol 3

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Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666201005143818 ◽

2020 ◽

Vol 20 ◽

Author(s):

Md. Junaid ◽

Yeasmin Akter ◽

Syeda Samira Afrose ◽

Mousumi Tania ◽

Md. Asaduzzaman Khan

Keyword(s):

Clinical Trials ◽

Signaling Pathways ◽

Signaling Pathway ◽

Inhibitory Effect ◽

Akt Signaling ◽

Review Article ◽

Therapeutic Drug ◽

Akt Signaling Pathway ◽

Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

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