Abstract
Objective: Synsepalum dulcificum Daniell. (SD) is a natural plant fruit and is famous for containing miraculin. It has been reported that SD can be used as an adjuvant treatment to correct patients' loss of taste during the antitumor process, but the effect of SD itself as an antitumor is not clear. In this study, we investigated the mechanism of action of SD on lung adenocarcinoma using network pharmacology. Materials and Methods. The components of SD were identified by liquid chromatography-mass spectrometry, and then the compounds that affect tumor immunity of SD were screened and the related targets were predicted by TCMIO database. At the same time, the results were associated with lung adenocarcinoma targets included in the MalaCards and CTD databases, so as to construct a compound-target action network diagram and explore the mechanism of SD in the treatment of lung adenocarcinoma. In in vitro experiments, cell viability was determined and western blotting was used to detect the related expression of action targets to determine the therapeutic effect of SD. Results. In this experiment, 335 chemical components were identified in SD, and 107 components were related to tumor immunity. After screening by ADME, it was found that 11 compounds might be inhaled into the human body and affect the growth of lung adenocarcinoma. In vitro experiments showed that SD could inhibit the growth of lung adenocarcinoma A549 cells. SD could reduce the expression of PCNA (P < 0.05) and significantly increase the expression of Caspase-3 (P < 0.05). The results of further experiments showed that SD could significantly reduce the phosphorylation of EGFR (P < 0.05), and SD could also effectively inhibit the expression of JAK and STAT3 phosphorylation (P < 0.01) and inhibit the expression of PI3K and AKT phosphorylation (P < 0.01). Conclusion. SD can inhibit the growth of lung adenocarcinoma A549 cells and the potential mechanism was found to be the inhibition of EGFR/JAK/STAT3 and EGFR/PI3K/AKT signaling pathway, and the substance basis for SD to exert antitumor effect may be catechin, taxifolin, betaine, epigallocatechin gallate, erucamide, guanosine, kaempferol, lanosterol, morin, oleanolic acid, and quercetin.
Highlights
Synsepalum dulcificum Daniell. (SD) can inhibit the growth of lung adenocarcinoma A549 cells and the potential mechanism was found to be the inhibition of EGFR/JAK/STAT3 and EGFR/phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, and the substance basis for SD to exert antitumor effect may be catechin, taxifolin, betaine, epigallocatechin gallate, erucamide, guanosine, kaempferol, lanosterol, morin, oleanolic acid, and quercetin
In order to further study the mechanism of SD affecting the growth of tumor cells, in the network pharmacology part, we have observed that the epidermal growth factor receptor signaling pathway is an important medium for SD affecting lung adenocarcinoma, and in the in vitro part, we have verified the mechanism of SD affecting the epidermal growth factor receptor-related pathways, focusing on EGFR/JAK/STAT and EGFR/PI3K/ AKT
We further found that SD significantly inhibited the phosphorylated expression of EGFR, which in turn inhibited the phosphorylated expression of JAK/STAT and PI3K/AKT. is indicated that SD had the effect of inhibiting the growth of lung adenocarcinoma cells, and the mechanism might be related to the inhibition of EGFR pathway
Summary
Synsepalum dulcificum Daniell. (SD) is a natural plant fruit and is famous for containing miraculin. Cell viability was determined and western blotting was used to detect the related expression of action targets to determine the therapeutic effect of SD. In vitro experiments showed that SD could inhibit the growth of lung adenocarcinoma A549 cells. E results of further experiments showed that SD could significantly reduce the phosphorylation of EGFR (P < 0.05), and SD could effectively inhibit the expression of JAK and STAT3 phosphorylation (P < 0.01) and inhibit the expression of PI3K and AKTphosphorylation (P < 0.01). SD can inhibit the growth of lung adenocarcinoma A549 cells and the potential mechanism was found to be the inhibition of EGFR/JAK/STAT3 and EGFR/PI3K/AKT signaling pathway, and the substance basis for SD to exert antitumor effect may be catechin, taxifolin, betaine, epigallocatechin gallate, erucamide, guanosine, kaempferol, lanosterol, morin, oleanolic acid, and quercetin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
