Center of Excellence for Dental Stem Cell Biology and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Oral Pathology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand.
Int J Mol Sci. 2024 Sep 25;25(19):10295. doi: 10.3390/ijms251910295.
Betaine, known as trimethylglycine, is a non-toxic natural substance reported to affect cancer cell responses. This study delves into the impact of betaine on the survival, proliferation, and invasion of oral squamous cell carcinoma (OSCC) cells in vitro. Human OSCC cells (HSC-4 and HSC-7) were subjected to varying concentrations of betaine, and their viability and proliferation were assessed through colourimetric MTT and colony-forming unit assays. Cell cycle progression and cell apoptosis were also investigated using flow cytometry, while cell migration and invasion were examined using a transwell migration assay, and the mRNA expression was evaluated by a quantitative polymerase chain reaction. Finally, proteomic analysis was conducted through liquid chromatography-tandem mass spectrometry on the extracted protein component of the cells. Results indicate that betaine effectively suppressed OSCC proliferation and colony formation. It triggered early apoptosis without disrupting cell cycle progression, reduced cell migration, and inhibited invasion. Betaine exposure led to significantly decreased mRNA levels of , , and while downregulating , a gene linked to epithelial-to-mesenchymal transition. Proteomic analysis revealed 9240 differentially expressed up/downregulated proteins in cells treated with betaine. The significantly upregulated proteins were associated with ATP-binding cassette (ABC) transporters, while the down-regulated proteins were associated with G protein-coupled receptors (GPCR) ligand binding. In conclusion, betaine exhibits potent anti-cancer properties by attenuating OSCC cell proliferation and mitigating invasion. Exploring this natural product as an adjunct for managing oral squamous cell carcinoma shows promise, although further investigations are needed to fully elucidate its functionality.
甜菜碱,又称三甲基甘氨酸,是一种无毒的天然物质,据报道可影响癌细胞的反应。本研究探讨了甜菜碱对体外口腔鳞状细胞癌(OSCC)细胞存活、增殖和侵袭的影响。将人 OSCC 细胞(HSC-4 和 HSC-7)暴露于不同浓度的甜菜碱中,通过比色 MTT 和集落形成单位测定法评估其活力和增殖。还通过流式细胞术研究细胞周期进展和细胞凋亡,通过 Transwell 迁移测定法检查细胞迁移和侵袭,通过定量聚合酶链反应评估 mRNA 表达。最后,通过细胞提取蛋白成分的液相色谱-串联质谱法进行蛋白质组学分析。结果表明,甜菜碱有效抑制了 OSCC 的增殖和集落形成。它引发早期凋亡,而不会破坏细胞周期进程,减少细胞迁移,并抑制侵袭。甜菜碱暴露导致基因 、 、 和 的 mRNA 水平显著降低,而与上皮间质转化相关的基因 下调。蛋白质组学分析显示,甜菜碱处理的细胞中有 9240 个差异表达的上调/下调蛋白。显著上调的蛋白与 ATP 结合盒(ABC)转运蛋白有关,而下调的蛋白与 G 蛋白偶联受体(GPCR)配体结合有关。总之,甜菜碱通过抑制 OSCC 细胞增殖和减轻侵袭来发挥强大的抗癌特性。尽管需要进一步研究来充分阐明其功能,但将这种天然产物作为管理口腔鳞状细胞癌的辅助手段具有很大的潜力。