Abstract

There are many studies in the literature on thymoquinone (TQ)-related cancer cells and models, and there is no relevant study investigating the efficacy of the oxime derivative of TQ (TQ-Ox). This study synthesized TQ-Ox and examined its cytotoxic, genotoxic and apoptotic properties in ovarian cancer cells. The structure TQ-Ox was confirmed with NMR. The cytotoxicity by luminometric ATP, intracellular reactive oxygen species (iROS) by fluorometric, intracellular calcium (iCa²⁺) by fluorometric, mitochondrial membrane potential (MMP) by flow cytometry, glutathione (GSH) levels with GSH/GSSG-Glo assay, DNA damage by comet assay, and apoptosis by acridine orange/ethidium bromide dye were determined. Concentrations of TQ-Ox were statistically increased cytotoxicity, DNA damage, apoptosis, iROS, and iCa²⁺ in a concentration-dependent manner (p < 0.001). Besides, MMP and GSH levels also decreased statistically significantly (p < 0.001) with increasing concentrations. TQ-Ox would be an effective treatment option by increasing cytotoxicity, genotoxicity, and apoptosis in ovarian carcinoma.

摘要

文献中有很多关于百里醌（TQ）相关癌细胞和模型的研究，目前还没有相关研究探讨TQ的肟衍生物（TQ-Ox）的功效。本研究合成了 TQ-Ox，并检查了其在卵巢癌细胞中的细胞毒性、基因毒性和凋亡特性。通过NMR确认结构TQ-Ox。通过发光 ATP 测定细胞毒性，通过荧光测定测定细胞内活性氧 (iROS)，通过荧光测定测定细胞内钙 (iCa ²⁺ )，通过流式细胞术测定线粒体膜电位 (MMP)，通过 GSH/GSSG-Glo 测定测定谷胱甘肽 (GSH) 水平，DNA通过彗星试验测定损伤，并通过吖啶橙/溴化乙锭染料测定细胞凋亡。TQ-Ox 的浓度以浓度依赖性方式显着增加细胞毒性、DNA 损伤、细胞凋亡、iROS 和 iCa ^{2+ (} p  < 0.001)。此外，随着浓度的增加，MMP 和 GSH 水平也显着下降（p  < 0.001）。TQ-Ox 通过增加卵巢癌的细胞毒性、基因毒性和细胞凋亡而成为一种有效的治疗选择。