Quzhou Hospital, Zhejiang University School of Medicine, Quzhou 324000, China; Department of Core Facility, Quzhou People's Hospital, Quzhou 324000, China.
Quzhou Hospital, Zhejiang University School of Medicine, Quzhou 324000, China; Zhejiang University School of Medicine, Hangzhou 310058, China.
Phytomedicine. 2021 Apr;84:153499. doi: 10.1016/j.phymed.2021.153499. Epub 2021 Feb 10.
There have been many researches on the effects of flavonoids on tumor treatment or adjuvant therapy, but there are few studies revealing their epigenetic effect on tumors. Hesperetin is a common citrus flavanone widely distributed among citrus fruits. The role of hesperetin in gastric cancer metastasis is unclear.
To investigate the effect of hesperetin on gastric cancer metastasis and its underlying mechanism.
We used cancer cell lines cultured in medium and nude mice implantation as in vitro and in vivo models to investigate the impact of hesperetin treatment on the migration and invasion of gastric cancer cells. The molecular biological experiments such as transwell assay, western blotting, qPCR, ChIP-qPCR, immunostaining and transfection were conducted to explore the molecular mechanisms.
We found that hesperetin obviously reduced the protein abundance of DOT1L and the methylation of histone H3K79 in a variety of cells. In gastric cancer cells, the treatment of hesperetin decreased cell migration and invasion and the expression of genes closely related to the metastatic capability. Mechanistically, hesperetin affected the stability of DOT1L protein by regulating the activity of CBP.
These findings highlight the epigenetic effect of hesperetin and provide a new perspective to understand the tumor suppressive effect of flavonoids.
已有许多研究探讨了类黄酮对肿瘤治疗或辅助治疗的影响，但很少有研究揭示其对肿瘤的表观遗传作用。橙皮素是一种常见的柑橘类黄酮，广泛存在于柑橘类水果中。橙皮素在胃癌转移中的作用尚不清楚。
研究橙皮素对胃癌转移的影响及其潜在机制。
我们使用培养在培养基中的癌细胞系和裸鼠植入作为体外和体内模型，研究橙皮素处理对胃癌细胞迁移和侵袭的影响。通过转染实验、western blot、qPCR、ChIP-qPCR、免疫组化等分子生物学实验，探索其分子机制。
我们发现橙皮素在多种细胞中明显降低了 DOT1L 蛋白丰度和组蛋白 H3K79 的甲基化。在胃癌细胞中，橙皮素处理降低了细胞迁移和侵袭能力以及与转移能力密切相关的基因表达。机制上，橙皮素通过调节 CBP 的活性影响 DOT1L 蛋白的稳定性。
这些发现强调了橙皮素的表观遗传作用，并为理解类黄酮的肿瘤抑制作用提供了新的视角。
