ABSTRACT
BACKGROUND: Modern pharmacological studies have shown that traditional Chinese medicine (TCM) Taraxacum mongolicum possesses anti-cancer activity. Taraxerol (TRX) is a pentacyclic triterpene isolated from T. mongolicum, which is widely used in clinical treatment, and its anti-cancer effects have been extensively studied. However, the effects and molecular mechanism of TRX in gastric cancer (GC) have not been fully explicated. METHODS: We used public databases to derive information on potential targets of TRX and proteins related to GC. Also, STRING and R3.6.2 software were used to analyze the protein-protein interaction (PPI). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were done to explain the potential mechanism underlying the regulatory role of TRX in GC. The role of TRX in GC was verified by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay, apoptosis analysis, Transwell assay, and wound healing assay, and the key signaling pathways were verified. RESULTS: We identified 135 potential targets for the treatment of GC via network pharmacological analysis. GO and KEGG enrichment analysis showed that steroid hormone receptor activity and the PI3K/AKT signaling pathway were the biological processes and pathways with the highest degree of enrichment. Additionally, cellular experiments revealed that TRX inhibited the proliferation, migration, and invasion of GC cells as well as induced G1 phase arrest and apoptosis in GC cells. CONCLUSION: Here, we used multi-target and multi-pathway network pharmacological analysis to verify the anti-cancer activity of TRX in GC. Also, in vitro experimental data were used to derive the potential molecular mechanism.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Oleanolic Acid/analogs & derivatives , Stomach Neoplasms/drug therapy , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Humans , Network Pharmacology , Oleanolic Acid/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Protein Interaction Maps , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolismABSTRACT
BACKGROUND: Pogostemon cablin is a traditional Chinese medicine (TCM) that is frequently used to treat various gastrointestinal diseases. Patchouli alcohol (PA), a compound extracted from the Pogostemon cablin, has been shown to have anti-tumor efficacy in human colorectal cancer. However, the mechanism of PA's anticancer effect on gastric cancer (GC) remains unknown. METHODS: We used the public database to obtain the potential targets of PA and genes related to GC. Bioinformatic analyses, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interactions (PPI), were used for analyzing the potential signal pathways and targets. Cell experiments were also conducted to further explain the impact and molecular mechanism of PA on GC, as well as to confirm the findings of network pharmacology. RESULTS: Using network pharmacological analysis, 161 possible targets were identified for the treatment of GC. Network analysis and functional enrichment analysis show that PA produced a marked effect in the treatment of GC through multi-targets and multi-pathways, especially the MAPK and PI3K/AKT signal pathways. In addition, PA showed the inhibition of GC cell proliferation, migration and invasion in cell experiments. According to our findings, PA could also cause G0/G1 phase arrest and apoptosis in GC cells. CONCLUSION: Using network pharmacology, we aim to uncover the possible molecular mechanism of PA on GC treatment in this research. Cell experiments were also conducted to confirm the therapeutic effect of PA on GC.
ABSTRACT
Qianjinweijing Tang (QJWJ) is a classic traditional Chinese formula that is often used in the treatment of treat lung cancer (LC). However, the underlying cellular mechanisms of the anticancer effects of QJWJ remain unclear. Cell viability was determined by MTS assay and levels of apoptosis measured by flow cytometry. Animal experiments were conducted to determine the effects of QJWJ on tumor growth in vivo. We used a proteomics approach to study the effects of QJWJ on LC cells and applied bioinformatics analysis to identify differentially expressed proteins that were validated by western blotting. QJWJ inhibited the proliferation of LC cells and induced apoptosis. The tumor growth delay effects of QJWJ were confirmed in vivo. We identified 104 differentially expressed proteins following QJWJ treatments of which 45 proteins were upregulated and 59 were downregulated. The levels of differentially expressed proteins were validated by western blotting. Our study indicated that QJWJ has anticancer effects in vivo and in vitro and that these effects are mediated by modulating the expression of tumor-related proteins.
Subject(s)
Antineoplastic Agents , Drugs, Chinese Herbal , Lung Neoplasms/metabolism , Proteome/drug effects , Proteomics/methods , A549 Cells , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Humans , Mice , Mice, Inbred BALB C , Proteome/analysis , Tandem Mass Spectrometry , Xenograft Model Antitumor AssaysABSTRACT
p-Hydroxylcinnamaldehyde isolated from the Cochinchina momordica seed (CMSP) has been identified to inhibit growth and metastasis in oesophageal squamous cell carcinoma (ESCC) by inducing differentiation. The aim of the present study was to evaluate the effect and underlying mechanism of CMSP on 4-nitroquinoline 1-oxide (4NQO)-induced oesophageal tumourigenesis. In the present study, a mouse model of oesophageal preneoplastic lesions was established by providing 4NQO-containing drinking water to C57BL/6 mice. The effect of CMSP on tumourigenesis induced by the chemical mutagen and the effect of CMSP on immune function were investigated. The results showed that the incidence and pathological stage of atypical hyperplasia in oesophageal tissues were significantly reduced in CMSP-treated mice compared with untreated mice. Immunohistochemistry and pull-down assay results revealed that the expression levels of p-ERK1/2, p-SAPK/JNK, and GTP-RhoA were significantly decreased in the oesophageal tissue of CMSP-treated mice. In addition, the proportions of CD4+ T cells, CD8+ T cells, and NK cells were increased, while the proportion of CD4+ CD25+ regulatory T cells (Tregs) was decreased, in the peripheral blood of CMSP-treated mice. These results indicated that CMSP could hamper 4NQO-induced oesophageal tumourigenesis by regulating the RhoA-ERK/JNK signaling pathway and promoting immune system function, thus providing a new potential strategy for treating preneoplastic lesions of the oesophagus.