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.

Background: Despite the critical progress of non-small cell lung cancer (NSCLC) therapeutic approaches, the clinical outcomes remain considerably poor. The requirement of developing novel therapeutic interventions is still urgent. In this study, we showed for the first time that diosbulbin C, a natural diterpene lactone component extracted from traditional Chinese medicine Dioscorea bulbifera L., possesses high anticancer activity in NSCLC. Methods: A549 and NCI-H1299 cells were used. The inhibitory effects of the diosbulbin C on NSCLC cell proliferation were evaluated using cytotoxicity, clone formation, EdU assay, and flow cytometry. Network pharmacology methods were used to explore the targets through which the diosbulbin C inhibited NSCLC cell proliferation. Molecular docking, qRT-PCR, and western blotting were used to validate the molecular targets and regulated molecules of diosbulbin C in NSCLC. Results: Diosbulbin C treatment in NSCLC cells results in a remarkable reduction in cell proliferation and induces significant G0/G1 phase cell cycle arrest. AKT1, DHFR, and TYMS were identified as the potential targets of diosbulbin C. Diosbulbin C may inhibit NSCLC cell proliferation by downregulating the expression/activation of AKT, DHFR, and TYMS. In addition, diosbulbin C was predicted to exhibit high drug-likeness properties with good water solubility and intestinal absorption, highlighting its potential value in the discovery and development of anti-lung cancer drugs. Conclusions: Diosbulbin C induces cell cycle arrest and inhibits the proliferation of NSCLC cells, possibly by downregulating the expression/activation of AKT, DHFR, and TYMS.

The disruption of zinc (Zn) homeostasis has been implicated in cancer development and progression through various signaling pathways. Maintaining intracellular zinc balance is crucial in the context of cancer. Human cells rely on two families of transmembrane transporters, SLC30A/ZNT and SLC39A/ZIP, to coordinate zinc homeostasis. While some ZNTs and ZIPs have been linked to cancer progression, limited information is available regarding the expression patterns of zinc homeostasis-related genes and their potential roles in predicting prognosis and developing therapeutic strategies for specific cancers. In this study, a systematic analysis was conducted to examine the expression of all genes from the SLC30A and SLC39A families at both mRNA and protein levels across different cancers. As a result, three SLC39A genes (SLC39A1, SLC39A4, and SLC39A8) were found to be significantly dysregulated in specific cancers, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), liver hepatocellular carcinoma (LIHC), pancreatic adenocarcinoma (PAAD), and kidney renal papillary cell carcinoma (KIRP). Moreover, the dysregulation of these genes was tightly associated with the prognosis of patients with those cancers. Furthermore, we found that the gene SLC39A8 exhibited the lowest mutation frequency in KIRP, whereas mutations in SLC39A4 were found to significantly impact overall survival (OS), disease-free (DF), and progress-free survival (PFS) in cancer patients, particularly in those with PAAD. Additionally, immune infiltration analysis revealed that SLC39A1, SLC39A4, and SLC39A8 may function as immune regulators in cancers. This provides new insights into understanding the complex relationship between zinc homeostasis and cancer progression.

Objective: Erianin has potential anticancer activities, especially against lung cancer. The specific mechanisms underlying the anti-cancer effects, including the molecular targets and signaling pathways in lung cancer, remain poorly understood and necessitate further investigation. Methods: Lung cancer cell viability was evaluated using the CCK-8 assay. Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression. mRNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes. Potential targets were identified and validated through molecular docking and Western blot analysis. The roles of mammalian target of rapamycin (mTOR) and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase (CAD) in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement. Additionally, lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo. Results: Erianin significantly inhibits the proliferation of lung cancer cells, induces apoptosis, and causes G₂/M phase cell cycle arrest. Integrative analysis of mRNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells. Notably, uridine supplementation mitigated the inhibitory effects of erianin, establishing a connection between pyrimidine metabolism and anticancer activity. Network pharmacology analyses identified mTOR as a key target of erianin. Erianin inhibited mTOR phosphorylation, thereby blocking downstream effectors (S6K and CAD), which are essential regulators of pyrimidine metabolism. Conclusions: Erianin is a promising therapeutic candidate for lung cancer. Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing mTOR activation.