Erianin, the main active ingredient of Dendrobium chrysotoxum Lindl, inhibits precancerous lesions of gastric cancer (PLGC) through suppression of the HRAS-PI3K-AKT signaling pathway as revealed by network pharmacology and in vitro experimental verification

Wang, Yan; Chu, Fuxiang; Lin, Jie; Li, Yuan; Johnson, Nadia; Zhang, Jianglan; Gai, Cong; Su, Zeqi; Cheng, Hongjie; Ding, Xia

doi:10.1016/j.jep.2021.114399

Cited by 49 publications

(39 citation statements)

References 52 publications

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“…According to a recently published study conducted in oral squamous cell carcinoma cells, erianin can induce both apoptosis and autophagy by regulating the MAPK signaling pathway, which has extensive cross talk with the PI3K/AKT/mTOR pathway ( Chen et al, 2020b ). Besides, erianin was found to be able to suppress hepatocellular carcinoma cells through downregulating PI3K/AKT and MAPK signaling pathways ( Yang et al, 2020a ) and inhibit gastric cancer cell growth through suppressing the HRAS–PI3K–AKT signaling pathway ( Wang et al, 2021 ). In fact, double targeting MAPK and PI3K cascades has been considered a rational combined therapeutic strategy in cancer therapy due to its vital role in regulating physiological processes and the limitation of single pathway inhibitors in clinical success ( Ciuffreda et al, 2014 ).…”

Section: Resultsmentioning

confidence: 99%

“…Actually, erianin has been reported to be able to downregulate the phosphorylation of JAK2 and STAT3 in 2LL cells, and thus inhibit the expression of several inflammatory mediators, such as COX-2 (cyclooxygenase-2), HIF-1α, and IL-6 (interleukin-6) ( Su et al, 2017 ). Moreover, PIK3CA, as one of most important regulatory molecules involved in PI3K–AKT and MAPK signaling pathways, has been frequently identified as a target of erianin in various cancers ( Yang et al, 2020a ; Wang et al, 2021 ; Xu et al, 2021 ; Zhang et al, 2021a ). According to KEGG pathway analysis, KIT, ERBB2, FLT3, PIK3CA, and RET are enriched in central carbon metabolism in cancer, while ABL1, CHEK2, and CCND1 are highly related to the cell cycle process, both of which are relatively less explored.…”

Section: Resultsmentioning

confidence: 99%

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Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology

Yan

Zhang

Liu

et al. 2022

Front. Mol. Biosci.

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Erianin is a major bisbenzyl compound extracted from Dendrobium chrysotoxum Lindl., an important traditional Chinese herb. In recent years, a growing body of evidence has proved the potential therapeutic effects of erianin on various cancers, including hepatoma, melanoma, non-small-cell lung carcinoma, myelogenous leukemia, breast cancer, and osteosarcoma. Especially, the pharmacological activities of erianin, such as antioxidant and anticancer activity, have been frequently demonstrated by plenty of studies. In this study, we firstly conducted a systematic review on reported anticancer activity of erianin. All updated valuable information regarding the underlying action mechanisms of erianin in specific cancer was recorded and summarized in this paper. Most importantly, based on the molecular structure of erianin, its potential molecular targets were analyzed and predicted by means of the SwissTargetPrediction online server (http://www.swisstargetprediction.ch). In the meantime, the potential therapeutic targets of 10 types of cancers in which erianin has been proved to have anticancer effects were also predicted via the Online Mendelian Inheritance in Man (OMIM) database (http://www.ncbi.nlm.nih.gov/omim). The overlapping targets may serve as valuable target candidates through which erianin exerts its anticancer activity. The clinical value of those targets was subsequently evaluated by analyzing their prognostic role in specific cancer using Kaplan-Meier plotter (http://Kmplot.com/analysis/) and Gene Expression Profiling Interactive Analysis (GEPIA) (http://gepia.cancer-pku.cn/). To better assess and verify the binding ability of erianin with its potential targets, molecular flexible docking was performed using Discovery Studio (DS). The valuable targets obtained from the above analysis and verification were further mapped to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway using the Database for Annotation, Visualization and Integrated Discovery (DAVID) (http://david.abcc.ncifcrf.gov/) to explore the possible signaling pathways disturbed/regulated by erianin. Furthermore, the in silico prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of erianin was also performed and provided in this paper. Overall, in this study, we aimed at 1) collecting all experiment-based important information regarding the anticancer effect and pharmacological mechanism of erianin, 2) providing the predicted therapeutic targets and signaling pathways that erianin might act on in cancers, and 3) especially providing in silico ADMET properties of erianin.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology

Yan

Zhang

Liu

et al. 2022

Front. Mol. Biosci.

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“…HRAS, an oncogene of the RAS family, is closely related to the proliferation, migration, invasion, and proangiogenic activity of gastric cancer cells. 25 ESR1 encodes estrogen receptor α (ER α) which can interact with other signaling molecules through multiple pathways, such as PI3K/AKT or MAPK signaling pathway. The ESR1 mutation was first reported in breast cancer, and it is associated with cell proliferation, metastasis and invasion in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Aloin Against Gastric Cancer

Gao¹,

Yang²,

Xie³

et al. 2022

DDDT

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This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental verification. Methods: Using network pharmacology methods, the potential targets of Aloin and targets related to GC were screened from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against GC. The expressions of major targets predicted by network pharmacology in normal stomach tissues and GC tissues and their relationships with overall survival of GC were searched in GEPIA, HPA and DriverDBv3 database. The results of network pharmacology analysis were verified by in vitro experiments. Results: A total of 129 potential targets were retrieved by searching the intersection of Aloin and GC targets. PPI network analysis indicated that 10 targets, including AKT1 and CASP3, were hub genes. GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anti-cancer effect of Aloin was mediated through multiple pathways, such as PI3K-AKT, FoxO and Ras signaling pathway. Among them, the PI3K-AKT signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of GC. The validation of key targets in GEPIA, HPA and DriverDBv3 database showed that the verification results for most core genes were consistent with this study. Then, the results of in vitro experiment indicated that Aloin could inhibit proliferation of NCI-N87 cells and induce cell apoptosis. The results also showed that Aloin could decrease the mRNA and protein expressions of PI3K and AKT, suggesting that Aloin can treat GC by inducing cell apoptosis and regulating the PI3K-AKT signaling pathway. Conclusion:This study identified the potential targets of Aloin against GC using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Aloin in treatment of GC.

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“…For example, it has been reported that Weifuchun (WFC) tablets can regulate the expression of oncogenes and tumor suppressor genes by regulating nuclear factor kappa B (NF-κB), runt-related transcription factor 3/transforming growth factor-β/Smad (RUNX3/TGF-β/Smad), Hh, mitogen-activated protein kinase (MAPK), and Wingless and int-1 (Wnt) signaling pathways ( 8 , 9 ). At the same time, erianin, the main active ingredient of Dendrobium officinale Kimura et Migo , inhibits PLGC through suppressing the Harvey rat sarcoma viral oncogene homolog/Phosphatidylinositol 3 Kinase/Protein Kinase B(HRAS/PI3K/AKT) signaling pathway ( 10 ). Similarly, the polysaccharides from D. candidum can reduce 8-OHdG levels and activate the NRF2 pathway and its related antioxidant enzymes HO-1 and NQO-1 to prevent PLGC and subsequent liver and kidney damage ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Study on the Mechanism of Sancao Tiaowei Decoction in the Treatment of MNNG-Induced Precancerous Lesions of Gastric Carcinoma Through Hedgehog Signaling Pathway

et al. 2022

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Sancao Tiaowei Decoction (SCTWD), a traditional Chinese medicine created by Professor Chen Weijian, has been used in the prevention and treatment of precancerous lesions of gastric carcinoma (PLGC). However, its mechanism has not been made clear. This study aimed to evaluate the therapeutic effect of SCTWD on 1-methyl-3-nitro-1-nitrosoguanidine-induced PLGC in rats and the mechanism of this effect. We found that SCTWD effectively repaired gastric mucosal injury, reversed the process of PLGC, and inhibited the occurrence of gastric cancer to some extent. In the results of hematoxylin-eosin (HE) staining, the number and arrangement of mucosal glands and the number of mononuclear cells in the lamina propria were improved in varying degrees; the enzyme-linked immunosorbent assay (ELISA) showed that the PG I and PGR of the medication treatment group were significantly higher; a Reverse Transcription-Polymerase Chain Reaction (RT-PCR) test showed that SCTWD could significantly upregulate the expression levels of Shh, Ptch, and Gli-1 in the gastric tissue of rats. The immunohistochemical method showed that SCTWD could significantly upregulate the protein expressions of Shh, Gli-1, Smo, cyclin D1, CDKN2A/p16INK4a, and NF-κBP65 and could reduce the expression of Ptch at the same time. Through the preliminary analysis of 75 compounds screened by UPLC-Q-TOF-MS, the main components, such as organic acids, esters and anhydrides, flavonoids, phenols, tanshinones, and so on, have anti-inflammatory and anti-tumor pharmacological effects. The results of KEGG enrichment analysis showed that 5 signaling pathways related to this project were found, and 33 differential genes were presented to construct the interaction network. These results suggested that SCTWD had a good regulatory effect on PLGC and thus may have a multi-targeted effect; SCTWD can not only significantly improve the pathological changes of gastric mucosa in rats with PLGC but also exert a strong effect of the regulation of the hedgehog signaling pathway.

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Erianin, the main active ingredient of Dendrobium chrysotoxum Lindl, inhibits precancerous lesions of gastric cancer (PLGC) through suppression of the HRAS-PI3K-AKT signaling pathway as revealed by network pharmacology and in vitro experimental verification

Cited by 49 publications

References 52 publications

Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology

Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology

Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Aloin Against Gastric Cancer

Study on the Mechanism of Sancao Tiaowei Decoction in the Treatment of MNNG-Induced Precancerous Lesions of Gastric Carcinoma Through Hedgehog Signaling Pathway

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