Faculty of Science and Technology, Gunma University, Kiryu 376-8515, Japan.
Graduate School of Nanobioscience, Yokohama City University, Yokohama 236-0027, Japan.
Genes (Basel). 2023 Feb 6;14(2):420. doi: 10.3390/genes14020420.
Natural antioxidants derived from plants exert various physiological effects, including antitumor effects. However, the molecular mechanisms of each natural antioxidant have not yet been fully elucidated. Identifying the targets of natural antioxidants with antitumor properties in vitro is costly and time-consuming, and the results thus obtained may not reliably reflect in vivo conditions. Therefore, to enhance understanding regarding the antitumor effects of natural antioxidants, we focused on DNA, one of the targets of anticancer drugs, and evaluated whether antioxidants, e.g., sulforaphane, resveratrol, quercetin, kaempferol, and genistein, which exert antitumor effects, induce DNA damage using gene-knockout cell lines derived from human Nalm-6 and HeLa cells pretreated with the DNA-dependent protein kinase inhibitor NU7026. Our results suggested that sulforaphane induces single-strand breaks or DNA strand crosslinks and that quercetin induces double-strand breaks. In contrast, resveratrol showed the ability to exert cytotoxic effects other than DNA damage. Our results also suggested that kaempferol and genistein induce DNA damage via unknown mechanisms. Taken together, the use of this evaluation system facilitates the analysis of the cytotoxic mechanisms of natural antioxidants.
植物来源的天然抗氧化剂具有多种生理作用，包括抗肿瘤作用。然而，每种天然抗氧化剂的分子机制尚未完全阐明。在体外鉴定具有抗肿瘤特性的天然抗氧化剂的靶标既昂贵又耗时，并且由此获得的结果可能无法可靠地反映体内条件。因此，为了增强对天然抗氧化剂抗肿瘤作用的理解，我们专注于 DNA，即抗癌药物的靶标之一，并评估了是否抗氧化剂，例如具有抗肿瘤作用的萝卜硫素、白藜芦醇、槲皮素、山奈酚和染料木黄酮，诱导用 DNA 依赖性蛋白激酶抑制剂 NU7026 预处理的人 Nalm-6 和 HeLa 细胞的基因敲除细胞系中的 DNA 损伤。我们的结果表明，萝卜硫素诱导单链断裂或 DNA 链交联，而槲皮素诱导双链断裂。相比之下，白藜芦醇显示出除 DNA 损伤以外的细胞毒性作用的能力。我们的结果还表明，山奈酚和染料木黄酮通过未知机制诱导 DNA 损伤。总之，该评估系统的使用有助于分析天然抗氧化剂的细胞毒性机制。
