Homodimers of Vanillin and Apocynin Decrease the Metastatic Potential of Human Cancer Cells by Inhibiting the FAK/PI3K/Akt Signaling Pathway

2017 ◽  
Vol 65 (11) ◽  
pp. 2299-2306 ◽  
Author(s):  
Phatcharida Jantaree ◽  
Kriengsak Lirdprapamongkol ◽  
Wilailak Kaewsri ◽  
Charnsak Thongsornkleeb ◽  
Kiattawee Choowongkomon ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Cancer ◽  
Metastatic Potential ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Human Cancer Cells

scholarly journals Pharmacological Manipulation of the Akt Signaling Pathway Regulates Myxoma Virus Replication and Tropism in Human Cancer Cells

2010 ◽  
Vol 84 (7) ◽  
pp. 3287-3302 ◽  
Author(s):  
Steven J. Werden ◽  
Grant McFadden
Keyword(s):  
Viral Replication ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Cancer ◽  
Akt Signaling ◽  
Myxoma Virus ◽  
Physical Interaction ◽  
Akt Signaling Pathway ◽  
Replication Efficiency ◽  
Human Cancer Cells

ABSTRACT Viruses have evolved an assortment of mechanisms for regulating the Akt signaling pathway to establish a cellular environment more favorable for viral replication. Myxoma virus (MYXV) is a rabbit-specific poxvirus that encodes many immunomodulatory factors, including an ankyrin repeat-containing host range protein termed M-T5 that functions to regulate tropism of MYXV for rabbit lymphocytes and certain human cancer cells. MYXV permissiveness in these human cancer cells is dependent upon the direct interaction between M-T5 and Akt, which has been shown to induce the kinase activity of Akt. In this study, an array of compounds that selectively manipulate Akt signaling was screened and we show that only a subset of Akt inhibitors significantly decreased the ability of MYXV to replicate in previously permissive human cancer cells. Furthermore, reduced viral replication efficiency was correlated with lower levels of phosphorylated Akt. In contrast, the PP2A-specific phosphatase inhibitor okadaic acid promoted increased Akt kinase activation and rescued MYXV replication in human cancer cells that did not previously support viral replication. Finally, phosphorylation of Akt at residue Thr308 was shown to dictate the physical interaction between Akt and M-T5, which then leads to phosphorylation of Ser473 and permits productive MYXV replication in these human cancer cells. The results of this study further characterize the mechanism by which M-T5 exploits the Akt signaling cascade and affirms this interaction as a major tropism determinant that regulates the replication efficiency of MYXV in human cancer cells.

scholarly journals Staurosporine suppresses survival of HepG2 cancer cells through Omi/HtrA2-mediated inhibition of PI3K/Akt signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769431 ◽  
Author(s):  
Youming Ding ◽  
Bin Wang ◽  
Xiaoyan Chen ◽  
Yu Zhou ◽  
Jianhui Ge
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Cancer ◽  
Akt Signaling ◽  
Therapeutic Effects ◽  
Concomitant Treatment ◽  
Dependent Manner ◽  
Akt Signaling Pathway

Staurosporine, which is an inhibitor of a broad spectrum of protein kinases, has shown cytotoxicity on several human cancer cells. However, the underlying mechanism is not well understood. In this study, we examined whether and how this compound has an inhibitory action on phosphatidylinositol 3-kinase (PI3K)/Akt pathway in vitro using HepG2 human hepatocellular carcinoma cell line. Cell viability and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxyribonucleotidyl transferase–mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, respectively. Glutathione S-transferase (GST) pull-down assay and co-immunoprecipitation were performed to detect protein–protein interactions. Small interfering RNA (siRNA) was used to silence the expression of targeted protein. We found that staurosporine significantly decreased cell viability and increased cell apoptosis in a concentration- and time-dependent manner in HepG2 cancer cells, along with the decreased expressions of PDK1 protein and Akt phosphorylation. Staurosporine was also found to enhance Omi/HtrA2 release from mitochondria. Furthermore, Omi/HtrA2 directly bound to PDK1. Pharmacological and genetic inhibition of Omi/HtrA2 restored protein levels of PDK1 and protected HepG2 cancer cells from staurosporine-induced cell death. In addition, staurosporine was found to activate autophagy. However, inhibition of autophagy exacerbated cell death under concomitant treatment with staurosporine. Taken together, our results indicate that staurosporine induced cytotoxicity response by inhibiting PI3K/Akt signaling pathway through Omi/HtrA2-mediated PDK1 degradation, and the process provides a novel mechanism by which staurosporine produces its therapeutic effects.

CNOT7 modulates biological functions of ovarian cancer cells via AKT signaling pathway

Life Sciences ◽  
2021 ◽  
Vol 268 ◽  
pp. 118996
Author(s):  
Jiangtao Yu ◽  
Xiaoli Hu ◽  
Xiuxiu Chen ◽  
Qiangyong Zhou ◽  
Qi Jiang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Ovarian Cancer Cells ◽  
Biological Functions ◽  
Akt Signaling Pathway

scholarly journals The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linwen Zhu ◽  
Zhe Li ◽  
Xiuchong Yu ◽  
Yao Ruan ◽  
Yijing Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Qrt Pcr

Abstract Background Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice. Results tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth. Conclusions tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.

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