<p>Chrysin Induced Cell Apoptosis and Inhibited Invasion Through Regulation of TET1 Expression in Gastric Cancer Cells</p>

Abstract

Ten-eleven translocation (TET) enzymes that oxidize a 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC) have been responsible for fine-tuning methylation patterns and exhibit role in epigenetic modifications. Chrysin, a natural flavone frequently present in honey, has been recognized to exhibit anti-tumor properties. In this study, we investigated the effects of Chrysin in the expression pattern of TET proteins in gastric cancer (GC) cells. Materials and Methods: Using qRT-PCR and Western blot analysis, we analyzed the expression of TET1 in GC cells in vitro following treatment with Chrysin. Immunofluorescence staining detected the expression levels of 5mC and 5hmC. Flow cytometry, wound healing, and Matrigel invasion assays were performed to determine cell proliferation, cell cycle, apoptosis, and migration and invasion of GC cells following treatment with Chrysin, si-TET1, and TET1-KO. Furthermore, a xenograft model was developed to analyze the expression pattern of TET1 on tumor development in vivo. Results: qRT-PCR and Western blot assays indicated that treatment with Chrysin significantly promoted the expression of TET1 in GC cells. Immunofluorescence study further confirmed that TET1 and 5hmC levels were significantly enhanced following treatment with Chrysin in MKN45 cells. Moreover, our results suggested that Chrysin could noticeably induce cell apoptosis and inhibit cell migration and invasion. Further, knockdown and overexpression of TET1 were conducted to investigate whether TET1 expression affected cell apoptosis, and cell migration and invasion in MKN45 cells. The results indicated that overexpression of TET1 markedly promoted cell apoptosis and inhibited cell migration and invasion. Furthermore, the TET1 gene knocked out was generated using the CRISPR/Cas9 system. Our data suggested that TET1 expression was associated with GC tumor growth in vivo. Conclusion: This study indicated that Chrysin exerted anti-tumor effects through the regulation of TET1 expression in GC and presented TET1 as a novel promising therapeutic target for GC therapy.

Antineoplastic Activity of Chrysin against Human Hepatocellular Carcinoma: New Insight on GPC3/SULF2 Axis and lncRNA-AF085935 Expression

“…According to our results of the MTT assay, which was used to examine the cell viability and proliferation, the present study reported dose- and time-dependent antiproliferative activity of chrysin alone and/or in combination with cisplatin in HepG2 cells confirming that chrysin could potentiate the antitumor activity of cisplatin. In a similar way, previous reports documented the antiproliferative effect of chrysin against different human cancers, such as ovarian [ 36 ], gastric [ 37 ], and colorectal [ 17 ] cancers, in addition to hepatocellular carcinoma cells [ 20 ].…”

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

“…In MKN45 cells, chrysin promotes the expression of TET1 and 5hmC to stimulate apoptosis and disrupt migration and invasion of GC cells. Furthermore, TET1 deletion by CRISPR/Cas9 system in a mouse model leads to the development of GC, and chrysin administration can be considered as a promising strategy in GC suppression [ 165 ].…”

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

“…The TGF-β can induce EMT and its inhibition by miR-145 suppresses malignant behavior of cancer cells ( Chen et al, 2020a ). Besides, silencing Linc00511 inhibits EMT and metastasis of cancer cells via TGF-β signaling down-regulation ( Zhong et al, 2020 ). The studies demonstrate that EMT regulation by TGF-β can participate in chemoresistance.…”