Apoptosis effect of Aegiceras corniculatum on human colorectal cancer via activation of FoxO signaling pathway

Luo, Hua; Hao, Erhong; Tan, Darren Qiancheng; Wei, Wei; Xie, Jinling; Feng, Xiaohui; Du, Zhenhong; Huang, Chun-Ying; Bai, Gang; Hou, Yuanyuan; Cheng, Chuanjing; Yi, Xiangxi; Wang, Ying; Hou, Xin; Deng, Jiagang

doi:10.1016/j.fct.2019.110861

Cited by 20 publications

(10 citation statements)

References 20 publications

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“…In the present study, we tested the role of different incubation durations of 1% O 2 in PC cells and confirmed that 24 h and 4 h of hypoxic incubation exerted the most effective promotion in PANC-1 and SW1990 cells, respectively. Our findings also indicated that hypoxia the induced migration and invasion of PC cells by promoting The FOXO family of transcription factors are regarded as tumor suppressors that mostly regulate cell proliferation, apoptosis, cell cycle arrest, and oxidative stress (28)(29)(30)(31). Numerous studies have reported that FOXO3a is inactivated in various cancers such as nasopharyngeal carcinoma, gastric cancer, breast cancer, hepatocellular carcinoma, ovarian cancer, lung cancer, and so on (32)(33)(34)(35)(36)(37).…”

Section: Discussionmentioning

confidence: 54%

Hypoxia promotes pancreatic cancer cell migration, invasion, and epithelial-mesenchymal transition via modulating the FOXO3a/ DUSP6/ERK axis

Zhao

Chen

Zhu

et al. 2021

J Gastrointest Oncol

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Background: Pancreatic cancer (PC) is among the most aggressive types of cancer. Hypoxia has been identified as a key risk factor for cancer progression. The forkhead box (FOX) proteins are multidirectional transcriptional factors that are strongly implicated in malignancies. However, whether FOXO3a, a member of the FOX protein family, is involved in the pro-oncogenic functions of hypoxia in PC has remained largely unelucidated. In this study, we attempted to clarify the role of FOXO3a in metastasis under hypoxic conditions and its underlying mechanism. Methods: MTT and flow cytometry assays were performed to detect the cell proliferation and cell cycle distribution respectively. Transwell assays were used to determine the potential of cell migration and invasion. qPCR and western blot assays were used to assess the expression of mRNA and protein. Immunofluorescence assay was performed to evaluate the cellular localization of FOXO3a. FOXO3a overexpression plasmid was constructed to perform the rescue experiment. Results: Our data indicated that PANC-1 and SW1990 cells represented enhanced cell migration and invasion abilities under hypoxia, while no statistical differences in cell proliferation and cell cycle distribution were observed. Hypoxia upregulated the messenger RNA (mRNA) and protein expressions of HIF-1α, FOXO3a, and the key epithelial-mesenchymal transition (EMT)-related (EMT) molecules N-cadherin and vimentin, as well as the phosphorylation of FOXO3a. Interestingly, hypoxia promoted the extranuclear localization of FOXO3a. Overexpression of FOXO3a not only significantly decreased the invasion, migration, and EMT of PC cell lines, but also reversed hypoxia-induced extranuclear localization. Finally, FOXO3a might act as a tumor suppressor in PC by inhibiting the ERK signaling pathway by inducing DUSP6 expression, and the ERK activator fisetin could effectively attenuate the inhibitory role of FOXO3a on ERK.Conclusions: Taken together, our results identified that hypoxia-induced extranuclear localization of FOXO3a promoted cell migration and invasion of human PC by modulating the DUSP6/ERK pathway.

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Section: Discussionmentioning

confidence: 54%

Hypoxia promotes pancreatic cancer cell migration, invasion, and epithelial-mesenchymal transition via modulating the FOXO3a/ DUSP6/ERK axis

Zhao

Chen

Zhu

et al. 2021

J Gastrointest Oncol

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“…Furthermore, we found that GEB may exert a therapeutic effect against CRC through other multiple signaling pathways. For instance, FoxO pathway(hsa04068) are involved in cell cycle regulation and proliferation process, activation of FoxO signaling pathway can induce apoptosis effect on human CRC [59]. The activation of the PI3K/AKT pathway(hsa04151) is known to have an important role in the development and progression of CRC, PI3K/AKT signaling leads to reduced apoptosis, stimulates cell growth and increases proliferation [60].…”

Section: Discussionmentioning

confidence: 99%

A network pharmacology-based investigation on the bioactive ingredients and molecular mechanisms of Gelsemium elegans Benth against colorectal cancer

Que

Chen

Yang

et al. 2021

BMC Complement Med Ther

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Background Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Gelsemium elegans Benth (GEB) is a traditional Chinese medicine commonly used for treatment for gastrointestinal cancer, including CRC. However, the underlying active ingredients and mechanism remain unknown. This study aims to explore the active components and the functional mechanisms of GEB in treating CRC by network pharmacology-based approaches. Methods Candidate compounds of GEB were collected from the Traditional Chinese Medicine@Taiwan, Traditional Chinese Medicines Integrated Database, Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine, and published literature. Potentially active targets of compounds in GEB were retrieved from SwissTargetPrediction databases. Keywords “colorectal cancer”, “rectal cancer” and “colon cancer” were used as keywords to search for related targets of CRC from the GeneCards database, then the overlapped targets of compounds and CRC were further intersected with CRC related genes from the TCGA database. The Cytoscape was applied to construct a graph of visualized compound-target and pathway networks. Protein-protein interaction networks were constructed by using STRING database. The DAVID tool was applied to carry out Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis of final targets. Molecular docking was employed to validate the interaction between compounds and targets. AutoDockTools was used to construct docking grid box for each target. Docking and molecular dynamics simulation were performed by Autodock Vina and Gromacs software, respectively. Results Fifty-three bioactive compounds were successfully identified, corresponding to 136 targets that were screened out for the treatment of CRC. Functional enrichment analysis suggested that GEB exerted its pharmacological effects against CRC via modulating multiple pathways, such as pathways in cancer, cell cycle, and colorectal cancer. Molecular docking analysis showed that the representative compounds had good affinity with the key targets. Molecular dynamics simulation indicated that the best hit molecules formed a stable protein-ligand complex. Conclusion This network pharmacology study revealed the multiple ingredients, targets, and pathways synergistically involved in the anti-CRC effect of GEB, which will enhance our understanding of the potential molecular mechanism of GEB in treatment for CRC and lay a foundation for further experimental research.

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“…Many phytochemicals are reported to display their anti-cancer activities by mediating the FoxO signaling pathway. For example, the extract of Aegiceras corniculatum induced apoptosis on human colorectal cancer via the FoxO signaling pathway (43). It is renowned that the FoxO signaling pathway exerts an enormous function in HCC etiology.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis Reveals the Anti-cancerous Mechanism of Licochalcone A on Human Hepatoma Cell HepG2

et al. 2021

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Hepatocellular carcinoma is a malignancy with a low survival rate globally, and there is imperative to unearth novel natural phytochemicals as effective therapeutic strategies. Licochalcone A is a chalcone from Glycyrrhiza that displayed various pharmacological efficacy. A globally transcriptome analysis was carried out to reveal the gene expression profiling to explore Licochalcone A's function as an anti-cancer phytochemical on HepG2 cells and investigate its potential mechanisms. Altogether, 6,061 dysregulated genes were detected (3,414 up-regulated and 2,647 down-regulated). SP1 was expected as the transcription factor that regulates the functions of most screened genes. GO and KEGG analysis was conducted, and the MAPK signaling pathway and the FoxO signaling pathway were two critical signal pathways. Protein-protein interaction (PPI) network analysis based on STRING platform to discover the hub genes (MAPK1, ATF4, BDNF, CASP3, etc.) in the MAPK signaling pathway and (AKT3, GADD45A, IL6, CDK2, CDKN1A, etc.) the FoxO signaling pathway. The protein level of essential genes that participated in significant pathways was consistent with the transcriptome data. This study will provide an inclusive understanding of the potential anti-cancer mechanism of Licochalcone A on hepatocellular, signifying Licochalcone A as a promising candidate for cancer therapy.

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Apoptosis effect of Aegiceras corniculatum on human colorectal cancer via activation of FoxO signaling pathway

Cited by 20 publications

References 20 publications

Hypoxia promotes pancreatic cancer cell migration, invasion, and epithelial-mesenchymal transition via modulating the FOXO3a/ DUSP6/ERK axis

Hypoxia promotes pancreatic cancer cell migration, invasion, and epithelial-mesenchymal transition via modulating the FOXO3a/ DUSP6/ERK axis

A network pharmacology-based investigation on the bioactive ingredients and molecular mechanisms of Gelsemium elegans Benth against colorectal cancer

Transcriptome Analysis Reveals the Anti-cancerous Mechanism of Licochalcone A on Human Hepatoma Cell HepG2

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