A Cell System-Assisted Strategy for Evaluating the Natural Antioxidant-Induced Double-Stranded DNA Break (DSB) Style

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.

 

Comments：

It is true that natural antioxidants derived from plants have been shown to have various physiological effects, including antitumor effects. However, the molecular mechanisms underlying these effects are not yet fully understood. Identifying the targets of natural antioxidants with antitumor properties in vitro is a challenging and time-consuming process, and the results may not accurately reflect the conditions in vivo.

To enhance our understanding of the antitumor effects of natural antioxidants, researchers have focused on DNA, one of the targets of anticancer drugs. They have evaluated whether natural antioxidants such as sulforaphane, resveratrol, quercetin, kaempferol, and genistein, which have been shown to exert antitumor effects, induce DNA damage using gene-knockout cell lines derived from human Nalm-6 and HeLa cells that were pretreated with the DNA-dependent protein kinase inhibitor NU7026.

The results of this study suggest that sulforaphane induces single-strand breaks or DNA strand crosslinks, and quercetin induces double-strand breaks. In contrast, resveratrol was found to have the ability to exert cytotoxic effects other than DNA damage. The study also suggests that kaempferol and genistein induce DNA damage through unknown mechanisms.

Overall, this evaluation system provides a useful tool for analyzing the cytotoxic mechanisms of natural antioxidants and may help to further our understanding of their antitumor effects.

Related Products

Cat.No.	Product Name	Information
S2893	NU7026	NU7026 (LY293646) is a potent DNA-PK inhibitor with IC50 of 0.23 μM in cell-free assays, 60-fold selective for DNA-PK than PI3K and inactive against both ATM and ATR. NU7026 enhances G2/M cell arrest and apoptosis.

Related Targets

PI3K Apoptosis related DNA-PK