Schlörmann Wiebke, Horlebein Christoph, Hübner Sabine M, Wittwer Elisa, Glei Michael
Department of Applied Nutritional Toxicology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Dornburger Straße 24, 07743 Jena, Germany.
Cancers (Basel). 2023 Jan 10;15(2):440. doi: 10.3390/cancers15020440.
The aim of the present study was to examine whether reactive oxygen species (ROS) contribute to chemopreventive effects of fermentation supernatants (FS) of different dietary fibers (Synergy1, oat-, barley-, yeast β-glucan, Curdlan) and butyrate as a fermentation metabolite. LT97 and HT29 cells were treated with butyrate and FS alone or with -acetyl-cysteine (NAC) and their impact on ROS formation, cell growth, and protein expression (Cyclin D2, p21, PARP, Bid, GPx2) was investigated. Butyrate and FS significantly decreased cell growth. ROS levels were significantly increased, particularly in LT97 cells, while co-treatment with NAC decreased ROS formation and growth inhibitory effects in both cell lines. After treatment with butyrate and FS, Cyclin D2 expression was reduced in LT97 cells and p21 expression was increased in both cell lines. Levels of full-length PARP and Bid were decreased, while levels of cleaved PARP were enhanced. GPx2 expression was significantly reduced by fiber FS in HT29 cells. A notable effect of NAC on butyrate- and FS-modulated protein expression was observed exclusively for PARP and Bid in HT29 cells. From the present results, a contribution of ROS to growth inhibitory and apoptotic effects of butyrate and FS on LT97 and HT29 cells cannot be excluded.
本研究的目的是检验活性氧(ROS)是否有助于不同膳食纤维(协同1、燕麦、大麦、酵母β-葡聚糖、凝胶多糖)的发酵上清液(FS)以及作为发酵代谢产物的丁酸盐的化学预防作用。分别用丁酸盐和FS单独处理或与N-乙酰半胱氨酸(NAC)共同处理LT97和HT29细胞,并研究它们对ROS形成、细胞生长和蛋白质表达(细胞周期蛋白D2、p21、聚(ADP-核糖)聚合酶(PARP)、BH3结构域凋亡诱导蛋白(Bid)、谷胱甘肽过氧化物酶2(GPx2))的影响。丁酸盐和FS显著降低细胞生长。ROS水平显著升高,尤其是在LT97细胞中,而与NAC共同处理可降低两种细胞系中的ROS形成和生长抑制作用。用丁酸盐和FS处理后,LT97细胞中细胞周期蛋白D2的表达降低,两种细胞系中p21的表达均升高。全长PARP和Bid的水平降低,而裂解的PARP水平升高。在HT29细胞中,纤维FS显著降低了GPx2的表达。仅在HT29细胞中观察到NAC对丁酸盐和FS调节的蛋白质表达有显著影响,作用于PARP和Bid。根据目前的结果,不能排除ROS对丁酸盐和FS对LT97和HT29细胞的生长抑制和凋亡作用有贡献。