Metastasis contributes a lot to cervical cancer high mortality rate. Icariside II is the principal component of Epimedium brevicornum Maxim and the major functional part to its therapeutic properties. However, the effects and mechanisms of Icariside II on cervical cancer metastasis remain unclear. Using female BALB/c mice with 60 mm3 tumors, we injected mice tail with 25 mg/kg body weight Icariside II or DMSO. After harvesting the tumor, immunohistochemistry and western blot were performed to detect MMP2/9 levels. Icariside II injection significantly inhibited MMP2/9 protein expression. The cell migration assays revealed that Icarisdie II inhibited the wound closure rate and the ability of Hela cell crossing the transwell chambers. Further, the key regulators in NF-κB and MAPK signaling pathway were detected in xenograft tumor and Hela cells by qPCR and western blot. JNK was screened out from several important signaling molecules, which had the same expression trend with MMP2/9. Finally, both 5 μM and 30 μM Icariside II weakened JNK-MMP2/9 signaling, despite the JNK activator Polyphyllin I and Anisomycin reversed the deficiencies. In this study, we proved that Icariside II can inhibit cervical cancer cells migration through JNK-MMP2/9 signaling pathway and is a prospective drug with high-chemopreventive effects on cervical cancer cell metastasis.
Colorectal carcinoma (CRC) is a major global health concern, with cancer metastasis being the main cause of patient mortality, and current CRC treatments are challenged by drug resistance. Although natural compounds, especially in foods like hawthorn proanthocyanidin extract (HPOE), have good anticancer activity, their effects on CRC metastasis remain unknown. Therefore, our objective was to investigate the impact and potential mechanisms of HPOE on the movement and infiltration of cells in the HCT116 CRC cells. Firstly, scratch-healing experiments confirmed the anti-migratory and anti-invasive capabilities of HPOE. Then, network pharmacology identified 16 possible targets, including MMP-9. Subsequently, RT-qPCR and Western blotting experiments confirmed that HPOE downregulated epithelial-mesenchymal transition-related factors (N-cadherin and MMP-9) and inhibited Wnt/β-catenin pathway activation. Finally, these results were experimentally validated using the Wnt pathway activator Licl and inhibitor XAV939. It was confirmed that HPOE had a certain inhibitory effect on the activation of the Wnt signaling pathway caused by the activator Licl and could enhance the inhibitory effect of the inhibitor XAV939. Our findings provide a basis for developing functional foods or dietary supplements, especially positioning HPOE as a functional food raw material for adjuvant treatment of CRC, given its ability to inhibit metastasis through the Wnt/β-catenin pathway.
Gamma-aminobutyric acid (GABA) is a nonprotein amino acid, which confers stress resistance to plants. Precise mechanisms underlying GABA accumulation in quinoa (Chenopodium quinoa) subjected to dark and ultrasonic stresses have not been elucidated. We conducted transcriptome and metabolome analyses of quinoa samples exposed to various stress treatments to reveal molecular pathways leading to GABA accumulation. Through the comprehensive integration of metabolome and transcriptome data, an association was revealed between GABA accumulation, 9 differentially expressed metabolites, and 27 differentially expressed genes. Two pathways responsible for GABA synthesis were identified, involving glutamate decarboxylase and aldehyde dehydrogenases, respectively. These enzymes regulate the enrichment of GABA in quinoa under dark and ultrasonic stress conditions. We demonstrated that under ultrasonic stress, proline and alanine increased, whereas glutamate and arginine declined. Phenolic acid, flavonoids, and alkaloid metabolites increased. These findings provide novel insights into the mechanism by which darkness and ultrasound stress enhance GABA, supporting the development of targeted synthetic biology techniques.