Pieńkowska Natalia, Bartosz Grzegorz, Furdak Paulina, Sadowska-Bartosz Izabela
Laboratory of Analytical Biochemistry, Institute of Food Technology and Nutrition, College of Natural Sciences, Rzeszow University, 4 Zelwerowicza Street, 35-601 Rzeszow, Poland.
Department of Bioenergetics, Food Analysis and Microbiology, Institute of Food Technology and Nutrition, College of Natural Sciences, Rzeszow University, 4 Zelwerowicza Street, 35-601 Rzeszow, Poland.
Int J Mol Sci. 2021 Jan 12;22(2):709. doi: 10.3390/ijms22020709.
3-Bromopyruvic acid (3-BP) is a promising anticancer compound. Two ovary cancer (OC) cell lines, PEO1 and SKOV3, showed relatively high sensitivity to 3-BP (half maximal inhibitory concentration (IC) of 18.7 and 40.5 µM, respectively). However, the further sensitization of OC cells to 3-BP would be desirable. Delphinidin (D) has been reported to be cytotoxic for cancer cell lines. We found that D was the most toxic for PEO1 and SKOV3 cells from among several flavonoids tested. The combined action of 3-BP and D was mostly synergistic in PEO1 cells and mostly weakly antagonistic in SKOV3 cells. The viability of MRC-5 fibroblasts was not affected by both compounds at concentrations of up to 100 µM. The combined action of 3-BP and D decreased the level of ATP and of dihydroethidium (DHE)-detectable reactive oxygen species (ROS), cellular mobility and cell staining with phalloidin and Mitotracker Red in both cell lines but increased the 2',7'-dichlorofluorescein (DCFDA)-detectable ROS level and decreased the mitochondrial membrane potential and mitochondrial mass only in PEO1 cells. The glutathione level was increased by 3-BP+D only in SKOV3 cells. These differences may contribute to the lower sensitivity of SKOV3 cells to 3-BP+D. Our results point to the possibility of sensitization of at least some OC cells to 3-BP by D.
3-溴丙酮酸（3-BP）是一种很有前景的抗癌化合物。两种卵巢癌细胞系PEO1和SKOV3对3-BP表现出相对较高的敏感性（半数最大抑制浓度（IC）分别为18.7和40.5μM）。然而，使卵巢癌细胞对3-BP进一步敏感化将是很有必要的。据报道，飞燕草素（D）对癌细胞系具有细胞毒性。我们发现，在几种测试的黄酮类化合物中，D对PEO1和SKOV3细胞毒性最大。3-BP和D的联合作用在PEO1细胞中大多是协同的，而在SKOV3细胞中大多是弱拮抗的。在浓度高达100μM时，两种化合物均未影响MRC-5成纤维细胞的活力。3-BP和D的联合作用降低了两种细胞系中ATP水平、二氢乙锭（DHE）可检测的活性氧（ROS）水平、细胞迁移能力以及用鬼笔环肽和线粒体红色荧光探针染色的细胞，但仅在PEO1细胞中增加了2',7'-二氯荧光素（DCFDA）可检测的ROS水平，并降低了线粒体膜电位和线粒体质量。仅在SKOV3细胞中，3-BP + D使谷胱甘肽水平升高。这些差异可能导致SKOV3细胞对3-BP + D的敏感性较低。我们的结果表明，D有可能使至少一些卵巢癌细胞对3-BP敏感化。
