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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. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore the mechanism by which hawthorn proanthocyanidins (HPC) inhibit cell proliferation and promote apoptosis in Huh-7 cells. Huh-7 cells and Traf6-overexpressed Huh-7 cells were cultured routinely at HPC concentrations of 0, 5, 10, 20, 40 and 80 μg/mL. Cell counting kit-8 (CCK-8) was used to detect the inhibitory effect of HPC on the proliferation of Huh-7 cells and Traf6-overexpressed Huh-7 cells. The mRNA expression of the tumor necrosis factor receptor associated factor 6 (Traf6), nuclear factor kappa-B p65 (NF-κB p65), Bax and caspase-3 genes were evaluated by real-time polymerase chain reaction (PCR). The protein expression of Traf6, NF-κB p65, Bax and caspase-3 were tested by Western blotting. Double staining with Annexin V-FITC and propidium iodide (PI) was used to test and calculate the apoptosis of Huh-7 cells. Treatment with HPC at concentrations higher than 20 μg/mL could inhibit Huh-7 cell proliferation in a dose-dependent way (P < 0.05). The over-expression of Traf6 promoted the proliferation of Huh-7 cells．Compared with the control group, HPC at 40 μg/mL significantly decreased the relative mRNA and protein expression of Traf6 and NF-κB p65 (P < 0.05), increased the relative mRNA and protein expression of Bax and caspase-3 (P < 0.05), and promoted Huh-7 cell apoptosis (P < 0.05). We concluded that HPC induce apoptosis in Huh-7 cells by down-regulating the Traf6/NF-κB signaling pathway.

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.

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Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)