Flavonoids have been reported to play an essential role in modulating processes of cellular redox homeostasis such as scavenging ROS. Meanwhile, they also induce oxidative stress that exerts potent antitumor bioactivity. However, the contradiction between these two aspects still remains unclear. In this study, four typical flavonoids were selected and studied. The results showed that low-dose flavonoids slightly promoted the proliferation of breast cancer cells under normal growth via gradually reducing accumulated oxidative products and demonstrated a synergistic effect with reductants NAC or VC. Besides, low-dose flavonoids significantly reduced the content of ROS and MDA induced by LPS or Rosup but restored the activity of SOD. However, high-dose flavonoids markedly triggered the cell death via oxidative stress as evidenced by upregulated ROS, MDA and downregulated SOD activity that could be partly rescued by NAC pretreatment, which was also confirmed by antioxidative gene expression levels. The underlying mechanism of such induced cell death was pinpointed as apoptosis, cell cycle arrest, accumulated mitochondrial superoxide, impaired mitochondrial function and decreased ATP synthesis. Transcriptomic analysis of apigenin and quercetin uncovered that high-dose flavonoids activated TNF-α signaling, as verified through detecting inflammatory gene levels in breast cancer cells and RAW 264.7 macrophages. Moreover, we identified that BRCA1 overexpression effectively attenuated such oxidative stress, inflammation and inhibited ATP synthesis induced by LPS or high dose of flavonoids possibly through repairing DNA damage, revealing an indispensable biological function of BRCA1 in resisting oxidative damage and inflammatory stimulation caused by exogenous factors.

(1) Background: Brown adipose tissue (BAT) burns energy to produce heat. Cyanidin-3-O-glucoside (C3G) can then enhance the thermogenic ability of BAT in vivo. However, the mechanism by which C3G regulates Ucp1 protein expression remains unclear. (2) Methods: In this study, C3H10T12 brown adipose cells and db/db mice and mice with high-fat, high-fructose, diet-induced obesity were used as the model to explore the effect of C3G on the expression of the Ucp1 gene. Furthermore, the 293T cell line was used for an in vitro cell transgene, a double luciferase reporting system, and yeast single hybridization to explore the mechanism of C3G in regulating Ucp1 protein. (3) Results: we identified that, under the influence of C3G, Prdm16 directly binds to the -500 to -150 bp promoter region of Ucp1 to activate its transcription and, thus, facilitate BAT programming. (4) Conclusions: This study clarified the mechanism by which C3G regulates the expression of the Ucp1 gene of brown fat to a certain extent.