scholarly journals Ganoderma tsugaeExtract Inhibits Growth of HER2-Overexpressing Cancer Cells via Modulation of HER2/PI3K/Akt Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Han-Peng Kuo ◽  
Shih-Chung Hsu ◽  
Chien-Chih Ou ◽  
Jhy-Wei Li ◽  
Hsiu-Hsueh Tseng ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Common Species ◽  
Biological Properties ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Her2 Protein

Ganoderma, also known as Lingzhi or Reishi, has been used for medicinal purposes in Asian countries for centuries. It is a medicinal fungus with a variety of biological properties including immunomodulatory and antitumor activities. In this study, we investigated the molecular mechanisms by whichGanoderma tsugae(GT), one of the most common species ofGanoderma, inhibits the proliferation of HER2-overexpressing cancer cells. Here, we show that a quality assured extract of GT (GTE) inhibited the growth of HER2-overexpressing cancer cellsin vitroandin vivoand enhanced the growth-inhibitory effect of antitumor drugs (e.g., taxol and cisplatin) in these cells. We also demonstrate that GTE induced cell cycle arrest by interfering with the HER2/PI3K/Akt signaling pathway. Furthermore, GTE curtailed the expression of the HER2 protein by modulating the transcriptional activity of theHER2gene and the stability/degradation of the HER2 protein. In conclusion, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of cancer cells that highly express HER2.

scholarly journals P4HA2 is associated with prognosis, promotes proliferation, invasion, migration and EMT in glioma

2020 ◽  
Author(s):  
Jing Lin ◽  
Xiao-Jun Wu ◽  
Wen-Xin Wei ◽  
Xing-Chun Gao ◽  
Ming-Zhu Jin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Tumor Xenograft ◽  
Receptor Interaction ◽  
Dependent Manner ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition

AbstractProlyl-4-hydroxylase subunit 2 (P4HA2), as a member of collagen modification enzymes, is induced under hypoxic conditions with essential roles in the collagen maturation, deposition as well as the remodeling of extracellular matrix(ECM). Mounting evidence has suggested that deregulation of P4HA2 is common in cancer. However, the expression pattern and molecular mechanisms of P4HA2 in glioma remain unknown. Here, we demonstrate that P4HA2 is overexpressed in glioma and inversely correlates with patient survival. Knockdown of P4HA2 inhibits proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT)-like phenotype of glioma cells in vitro and suppressed tumor xenograft growth in vivo. Mechanistically, bioinformatics analysis shows that ECM-receptor interaction and PI3K/AKT pathway are the most enriched pathways of the co-expressed genes with P4HA2. Furthermore, P4HA2 mRNA was positively correlated with mRNA expressions of a series of collagen genes, but not mRNA of PI3K or AKT1/2. Conversely, both the protein expressions of collagens and phosphorylated PI3K/AKT could be downregulated either by silencing of P4HA2 expression or inhibition of its prolyl hydroxylase. Moreover, the inhibitory effects on the migration, invasion and the EMT-related molecules by P4HA2 knockdown can be recapitulated by the Akt phosphorylation activator. Taken together, our findings for the first time reveal an oncogenic role of P4HA2 in the glioma malignancy. By regulating the expression of fibrillar collagens and the downstream PI3K/AKT signaling pathway, it may serve as a potential anti-cancer target for the treatment of glioma.HighlightsP4HA2 is overexpressed and correlated with poor prognosis in glioma.P4HA2 depletion inhibits glioma proliferation, migration, invasion and EMT-like phenotype in vitro and tumorigenesis in vivo.P4HA2 depletion attenuates the PI3K/AKT signaling pathway in a collagen-dependent manner.

A77 1726 (leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice

2018 ◽  
Vol 132 (6) ◽  
pp. 685-699 ◽  
Author(s):  
Zhen-Guo Ma ◽  
Xin Zhang ◽  
Yu-Pei Yuan ◽  
Ya-Ge Jin ◽  
Ning Li ◽  
...  
Keyword(s):  
T Cell ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Akt Signaling ◽  
Akt Signaling Pathway

T-cell infiltration and the subsequent increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure (HF). A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cell-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II (Ang II)-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro. In addition, we showed that A77 1726 administration prevented induction of cardiac fibrosis by inhibiting cardiac fibroblast (CF) transformation into myofibroblast. Surprisingly, we found that the protective effect of A77 1726 was not dependent on its T lymphocyte-inhibiting property. A77 1726 suppressed the activation of protein kinase B (AKT) signaling pathway, and overexpression of constitutively active AKT completely abolished A77 1726-mediated cardioprotective effects in vivo and in vitro. Pretreatment with siRNA targetting Fyn (si Fyn) blunted the protective effect elicited by A77 1726 in vitro. More importantly, A77 1726 was capable of blocking pre-established cardiac hypertrophy in mice. In conclusion, A77 1726 attenuated cardiac hypertrophy and cardiac fibrosis via inhibiting FYN/AKT signaling pathway.

Cyanidin inhibits EMT induced by oxaliplatinviatargeting the PDK1–PI3K/Akt signaling pathway

2019 ◽  
Vol 10 (2) ◽  
pp. 592-601 ◽  
Author(s):  
Xiang Li ◽  
Ze-sheng Zhang ◽  
Xiao-han Zhang ◽  
Sheng-nan Yang ◽  
Dong Liu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Anthocyanins have been shown to exhibit antitumor activity in several cancersin vitroandin vivo.

scholarly journals Luteolin Exerts Cardioprotective Effects through Improving Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats during Ischemia/Reperfusion In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Changsheng Nai ◽  
Haochen Xuan ◽  
Yingying Zhang ◽  
Mengxiao Shen ◽  
Tongda Xu ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Signaling Pathway ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Myocardial Infarct Size ◽  
Akt Signaling Pathway ◽  
Cardioprotective Effects

The flavonoid luteolin exists in many types of fruits, vegetables, and medicinal herbs. Our previous studies have demonstrated that luteolin reduced ischemia/reperfusion (I/R) injury in vitro, which was related with sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. However, the effects of luteolin on SERCA2a activity during I/R in vivo remain unclear. To investigate whether luteolin exerts cardioprotective effects and to monitor changes in SERCA2a expression and activity levels in vivo during I/R, we created a myocardial I/R rat model by ligating the coronary artery. We demonstrated that luteolin could reduce the myocardial infarct size, lactate dehydrogenase release, and apoptosis during I/R injury in vivo. Furthermore, we found that luteolin inhibited the I/R-induced decrease in SERCA2a activity in vivo. However, neither I/R nor luteolin altered SERCA2a expression levels in myocardiocytes. Moreover, the PI3K/Akt signaling pathway played a vital role in this mechanism. In conclusion, the present study has confirmed for the first time that luteolin yields cardioprotective effects against I/R injury by inhibiting the I/R-induced decrease in SERCA2a activity partially via the PI3K/Akt signaling pathway in vivo, independent of SERCA2a protein level regulation. SERCA2a activity presents a novel biomarker to assess the progress of I/R injury in experimental research and clinical applications.

scholarly journals Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by targeting the AKT signaling pathway

2018 ◽  
Vol 36 (5) ◽  
pp. 743-754 ◽  
Author(s):  
Piming Zhao ◽  
Ana E. Aguilar ◽  
Joanna Y. Lee ◽  
Lucy A. Paul ◽  
Jung H. Suh ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Therapeutic Efficacy ◽  
Akt Signaling ◽  
Akt Signaling Pathway

PTEN improve renal fibrosis in vitro and in vivo through inhibiting FAK/AKT signaling pathway

2019 ◽  
Vol 120 (10) ◽  
pp. 17887-17897 ◽  
Author(s):  
Yongchao Du ◽  
Peihua Liu ◽  
Zhi Chen ◽  
Yao He ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Akt Signaling ◽  
Akt Signaling Pathway
Sign in / Sign up

Export Citation Format

Share Document