stigmasterol and Ovarian-Neoplasms

This study was aimed at exploring the regulatory mechanism of Xiaoyao San (XYS) and its main compound, Stigmasterol, in the biological network and signaling pathway of ovarian cancer (OC) through network pharmacology-based analyses and experimental validation.. The active compounds and targets of XYS were studied by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The GeneCards and OMIM databases were used to screen common targets of XYS in the treatment of OC. Combined with the STRING database and Cytoscape 3.6.0, the core compounds and targets of XYS were obtained. GO and KEGG pathway enrichment analyses of core target genes were carried out by using the Metascape and DAVID databases. Molecular docking has been achieved by using the AutoDock Vina program to discuss the interaction of the core targets and compounds of XYS in the treatment of OC. The effect of Stigmasterol on proliferation and migration were assessed by CCK8 and wound healing assay. Western blot and qRT-PCR were used to analyze the protein and mRNA expressions of PI3K, Akt, and PTEN after treatment of Stigmasterol.. A total of 113 common targets of XYS for the treatment of OC were obtained from 975 targets related to OC and 239 targets of XYS's effect. The main compounds of XYS include Quercetin, Naringenin, Isorhamnetin, and Stigmasterol, which mainly regulate the targets such as TP53, Akt1, and MYC and PI3K/Akt, p53, and cell cycle signal pathways. At the same time, molecular docking showed that Stigmasterol and Akt1 had good docking conformation. Stigmasterol inhibited OC cell proliferation and migration in vitro and reduced the protein and mRNA expressions of the PI3K/Akt signaling pathway.. Stigmasterol as the one of the main compounds of XYS suppresses OC cell activities through the PI3K-Akt signaling pathway.

Topics: Blotting, Western; Drugs, Chinese Herbal; Female; Humans; Molecular Docking Simulation; Network Pharmacology; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Stigmasterol

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Disease Models, Animal; Endoplasmic Reticulum Stress; Female; Humans; Mitochondria; Oceans and Seas; Ovarian Neoplasms; Phaeophyceae; Stigmasterol; Zebrafish

Topics: Apoptosis; Breast Neoplasms; Female; Ganoderma; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Ovarian Neoplasms; Stigmasterol; Tumor Suppressor Protein p53