Mechanism of action of icaritin on uterine corpus endometrial carcinoma based on network pharmacology and experimental evaluation

Abstract

BackgroundUterine corpus endometrial carcinoma (UCEC) belongs to a group of epithelial malignant tumors. Icaritin is the main active compound of Epimedii Folium. Icaritin has been utilized to induce UCEC cells to death.MethodsWe wished to identify potential targets for icaritin in the treatment of UCEC, as well as to provide a groundwork for future studies into its pharmacologic mechanism of action. Network pharmacology was employed to conduct investigations on icaritin. Target proteins were chosen from the components of icaritin for UCEC treatment. A protein–protein interaction (PPI) network was established using overlapping genes. Analyses of enrichment of function and signaling pathways were undertaken using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, to select “hub genes”. Finally, experiments were carried out to ascertain the effect of icaritin on endometrial cancer (HEC-1-A) cells.ResultsWe demonstrated that icaritin has bioactive components and putative targets that are therapeutically important. Icaritin treatment induced sustained activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt pathway) and inhibited growth of HEC-1-A cells.ConclusionOur data provide a rationale for preclinical and clinical evaluations of icaritin for UCEC therapy.

Extraction, purification and anticancer activity studies on triterpenes from pomegranate peel

“…Jin et al used a network pharmacology method for selecting “hub genes” to identify potential targets for icaritin in the treatment of endometrial cancer (HEC-1-A). 34 The experimental results indicated that icaritin treatment induced the sustained activation of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt pathway) and inhibited the growth of HEC-1-A cells. In this study, network pharmacology was used to predict the anticancer targets and pathways of the main triterpenes contained in TPP.…”

Advancements in the Biotransformation and Biosynthesis of the Primary Active Flavonoids Derived from Epimedium

“…Icaritin possesses diverse pharmacological activities [51], including protection of neurons against amyloid-induced neurotoxicity [52], promotion of differentiation from embryonic stem cells into cardiomyocytes [53], anti-osteoporosis effects and osteogenesis promotion [54,55], immunomodulation [56,57], and recovery of UVB-induced photoaging of human keratinocytes [58]. Moreover, icaritin is considered as a promising candidate for the treatment of various cancers [59,60], including hepatocellular carcinoma [61][62][63], breast cancer [64], lung cancer [65], ovarian cancer [66], endometrial cancer [67], human oral squamous cell carcinoma [68], and multiple hematological malignancies [59,[69][70][71]. In the treatment of hepatocellular carcinoma, icaritin can suppress cell growth and promote cell apoptosis via down-regulating alpha-fetoprotein gene expression in hepatocellular carcinoma [62] and inducing anti-tumor immune responses [61,63].…”