Anti-Tumor Activity of Yuanhuacine by Regulating AMPK/mTOR Signaling Pathway and Actin Cytoskeleton Organization in Non-Small Cell Lung Cancer Cells

Kang, Ja Heon; Hong, Ji‐Young; Lee, Hyejung; Bae, Song Yi; Jung, Cholomi; Park, Hyen Joo; Lee, Sang Kook

doi:10.1371/journal.pone.0144368

Cited by 42 publications

(32 citation statements)

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“…thus, The utilization of AMPK or perhaps the regulation of downstream targets may provide potential therapeutic targets in the treatment of prostate cancer41. Of note, in line with our results, the compound C directly inhibition of the phosphorylation of AMPK itself have been reported in several other studies424344. Concerning an additional feedback role, the effects of compound C on AMPK signaling could be more complicated then we thought.…”

Section: Discussionsupporting

confidence: 86%

Activation of AMPKα mediates additive effects of solamargine and metformin on suppressing MUC1 expression in castration-resistant prostate cancer cells

Xiang

Zhang

Tang

et al. 2016

Sci Rep

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Prostate cancer is the second most common cause of cancer-related deaths worldwide. The mucin 1 (MUC1) oncoprotein is highly expressed in human prostate cancers with aggressive features. However, the role for MUC1 in occurrence and progression of castration-resistant prostate cancer (CRPC) remained elusive. In this study, we showed that solamargine, a major steroidal alkaloid glycoside, inhibited the growth of CRPC cells, which was enhanced in the presence of metformin. Furthermore, we found that solamargine increased phosphorylation of AMPKα, whereas reducing the protein expression and promoter activity of MUC1. A greater effect was observed in the presence of metformin. In addition, solamargine reduced NF-κB subunit p65 protein expression. Exogenously expressed p65 resisted solamargine-reduced MUC1 protein and promoter activity. Interestingly, exogenously expressed MUC1 attenuated solamargine-stimulated phosphorylation of AMPKα and, more importantly reversed solamargine-inhibited cell growth. Finally, solamargine increased phosphorylation of AMPKα, while inhibiting MUC1, p65 and tumor growth were observed in vivo. Overall, our results show that solamargine inhibits the growth of CRPC cells through AMPKα-mediated inhibition of p65, followed by reduction of MUC1 expression in vitro and in vivo. More importantly, metformin facilitates the antitumor effect of solamargine on CRPC cells.

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Section: Discussionsupporting

confidence: 86%

Activation of AMPKα mediates additive effects of solamargine and metformin on suppressing MUC1 expression in castration-resistant prostate cancer cells

Xiang

Zhang

Tang

et al. 2016

Sci Rep

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show abstract

“…110 Excitingly, new drugs, such as Yuanhuacine, have shown mTORC2 inhibition in vitro . 111 Additionally, development of small molecular inhibitors has resulted in the generation of P7170, which has shown mTORC1 and 2 inhibition in cancer cell lines. 112 The equilibrium between these 2 complexes is essential because inhibiting mTORC1 may, in fact, promote upregu-lation of mTORC2 signaling.…”

Section: Implication Of Targeting Mtor Signaling In Lung Cancermentioning

confidence: 99%

Targeting the Mammalian Target of Rapamycin in Lung Cancer

Vicary

Roman

2016

The American Journal of the Medical Sciences

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Lung cancer is the leading cause of cancer death worldwide. Despite advances in its prevention and management, the prognosis of patients with lung cancer remains poor. Therefore, much attention is being given to factors that contribute to the development of this disease, the mechanisms that drive oncogenesis and tumor progression and the search for novel targets that could lead to the development of more effective treatments. One cellular pathway implicated in lung cancer development and progression is that of the mammalian target of rapamycin. Studies involving human tissues have linked lung cancer with abnormalities in this pathway. Furthermore, studies in vitro and in vivo using animal models of lung cancer reveal that targeting this pathway might represent an effective means of treating this disease. As a result, there is significant effort invested in the development of drugs targeting mammalian target of rapamycin and related pathways in the clinical setting.

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“…As reported, Song et al [24] found that AEG-1 can promote glycolysis and tumorigenesis in colorectal carcinoma cells via AMPK signaling. Also, several studies have revealed that AMPK signaling pathway played a significant role in energy metabolism and NSCLC [25–27]. In our current study, we hypothesized that AEG-1 could play an important role in NSCLC via AMPK signaling pathway, but the authentic underlying mechanism of AEG-1 in NSCLC still needs to be investigated with a further research.…”

Section: Discussionmentioning

confidence: 78%

Clinical significance and effect of AEG-1 on the proliferation, invasion, and migration of NSCLC: a study based on immunohistochemistry, TCGA, bioinformatics, in vitro and in vivo verification

Zhang

Hou

et al. 2017

Oncotarget

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BackgroundAstrocyte elevated gene-1 (AEG-1) is related to the tumorigenesis and deterioration of different cancers, including non-small cell lung cancer (NSCLC). However, the effect of AEG-1 in NSCLC remains unclear. In this study, we aimed to investigate the clinical significance and effect of AEG-1 on biological function of NSCLC.ResultsAEG-1 was significantly overexpressed in NSCLC tissues and closely correlated to the deterioration of NSCLC based on tissue microarray, TCGA database and meta-analysis. After knock-down of AEG-1, the proliferation, migration and invasion of NSCLC cells were all inhibited, and the tumorigenic and angiogenic ability of NSCLC cells were weakened. Furthermore, the AEG-1 co-expressed genes were significantly related to AMPK signaling pathway based on bioinformatics approaches.Materials and MethodsA tissue microarray, the Cancer Genome Atlas (TCGA) database, as well as a meta-analysis were performed to analyze the relationship between AEG-1 and the clinicopathological parameters of NSCLC. Furthermore, immunocytochemistry, Western blot analysis, scratch assay, colony formation assay, Transwell migration and invasion assay and the chick embryo chorioallantoic membrane (CAM) model were conducted to explore the effect of AEG-1 on NSCLC in vitro and in vivo. Additionally, bioinformatics analyses were carried out to assess the potential pathways and networks of the co-expressed genes of AEG-1.ConclusionsAEG-1 is positively activated in the tumorigenesis and deterioration of NSCLC. We hypothesize that AEG-1 could play an important role in NSCLC via AMPK signaling pathway. Inhibiting the expression of AEG-1 is expected to become a novel method in the therapeutic strategies of NSCLC.

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Anti-Tumor Activity of Yuanhuacine by Regulating AMPK/mTOR Signaling Pathway and Actin Cytoskeleton Organization in Non-Small Cell Lung Cancer Cells

Cited by 42 publications

References 50 publications

Activation of AMPKα mediates additive effects of solamargine and metformin on suppressing MUC1 expression in castration-resistant prostate cancer cells

Activation of AMPKα mediates additive effects of solamargine and metformin on suppressing MUC1 expression in castration-resistant prostate cancer cells

Targeting the Mammalian Target of Rapamycin in Lung Cancer

Clinical significance and effect of AEG-1 on the proliferation, invasion, and migration of NSCLC: a study based on immunohistochemistry, TCGA, bioinformatics, in vitro and in vivo verification

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