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The Cytotoxic Effects of Geranylgeranylacetone Are Attenuated in the High-Glucose Condition

机译:在高葡萄糖条件下减弱了香叶基香叶基丙酮的细胞毒作用。

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Geranylgeranylacetone (GGA) has been used as an antiulcer drug and also is known as inducer of heat shock protein 70 that has cytoprotective effects especially in hyperglycemic condition. In contrast, cytotoxicity of GGA has also been reported. Some studies have reported that GGA suppresses cell growth and induces apoptosis in cell models of human leukemia, ovarian carcinoma, and colon cancer in vitro . Therefore, the aim of this study was to determine whether GGA can have a cytotoxic effect on a human cervical cancer cell line (HeLa), human colorectal adenocarcinoma cells (Caco-2), and human embryonic kidney cells 293 (HEK) in normal-glucose and high-glucose environments (NG and HG, respectively). The results showed that 100?μM GGA inhibited proliferation of HeLa cells only in NG environment despite inhibiting proliferation of Caco-2 and HEK cells regardless of glucose concentration. Cell viability assay revealed that GGA decreased viability of HeLa, Caco-2, and HEK cells only in NG environment. Flow cytometric analyses revealed that the type of cell death was a combination of necrosis and apoptosis. Our study revealed that difference in cytotoxicity of GGA is influenced by glucose condition. The cytotoxic effects of GGA are attenuated in the HG condition. Since both cytotoxic and cytoprotective effects are reported about GGA, further research is needed about the mechanism of the cytotoxic effects.
机译:Geranylgeranylacetone(GGA)已被用作抗溃疡药,并且也被称为热休克蛋白70的诱导剂,该蛋白具有细胞保护作用,尤其是在高血糖情况下。相反,也已经报道了GGA的细胞毒性。一些研究报道,GGA在体外在人白血病,卵巢癌和结肠癌的细胞模型中抑制细胞生长并诱导细胞凋亡。因此,这项研究的目的是确定在正常情况下,GGA对人宫颈癌细胞系(HeLa),人结肠直肠腺癌细胞(Caco-2)和人胚胎肾细胞293(HEK)是否具有细胞毒性作用。葡萄糖和高葡萄糖环境(分别为NG和HG)。结果表明,无论葡萄糖浓度如何,100μmGGA均能抑制Caco-2和HEK细胞的增殖,但仅在NG环境下能抑制HeLa细胞的增殖。细胞活力测定表明,GGA仅在NG环境下会降低HeLa,Caco-2和HEK细胞的活力。流式细胞仪分析表明,细胞死亡的类型是坏死和凋亡的组合。我们的研究表明,GGA的细胞毒性差异受葡萄糖状况的影响。在HG条件下,GGA的细胞毒性作用减弱。由于有关GGA的细胞毒性和细胞保护作用均已报道,因此需要进一步研究其细胞毒性作用的机理。

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