Apoptosis induction in human prostate cancer cells related to the fatty acid metabolism by wogonin-mediated regulation of the AKT-SREBP1-FASN signaling network.

Prostate cancer (PCa) cells exploit cellular metabolic reprogramming as their survival advantage, especially aberrant lipid signaling and metabolism. Although recent studies deemed that PCa tends to rely on lipid fuel in comparison with aerobic glycolysis, the relationship between lipid metabolism and cancer growth remains unknown. We demonstrated that wogonin, a naturally occurring mono-flavonoid, could induce apoptosis of PCa cells in vivo and in vitro. Mechanistically, 100 µM wogonin significantly increased the expression of proteins related to the fatty acid synthesis and accumulation as a result of stimulation of AKT phosphorylation and nuclear accumulation of sterol regulatory element-binding protein 1 (SREBP1). The wogonin-induced up-regulation of fatty acid synthase (FASN) promoted fatty acid synthesis and storage, while increased oxidation in mitochondria driven by carnitine palmitoyl-transferase 1A (CPT1A) resulted in the loss of mitochondrial membrane potential and reactive oxygen species (ROS) accumulation, ultimately inducing apoptosis in DU145 and 22Rv1 cells. In vivo, 100 mg/kg of wogonin (i.v.) significantly repressed tumor growth without any obvious toxicity in the PCa xenograft model. In short, we proved that wogonin regulated the fatty acid metabolism and induced apoptosis by activating the AKT-SREBP1-FASN signaling network in human PCa cells, and it exhibited potent anti-tumor effects both in vivo and vitro. Thus it might be a promising candidate for the development of anti-cancer drugs.

Interactions between salicylic acid and antioxidant enzymes tilting the balance of H2O2 from photorespiration in non-target crops under halosulfuron-methyl stress.

Halosulfuron-methyl (HSM) is a safe, selective and effective sulfonylurea herbicide (SU) for the control of sedge and broadleaf weeds in sugarcane, corn, tomato, and other crops. The primary site of action is acetolactate synthase (ALS), a key enzyme of branched chain amino acids (BCAAs) synthesis. In addition to ALS inhibition, BCAAs deficiencies and oxidative damage may be involved in toxic effects of SUs. However, secondary targets of HSM relevant to plant physiological responses are unclear. In the present study, comparative growth inhibition and peroxidization injury between sensitive and tolerance crops were observed at biochemical and physiological levels suggesting involvement of H2O2, ethylene, salicylic acid (SA) in the oxidative stress responses to HSM. HSM caused accumulation of H2O2, stimulated photorespiration and consequent accumulation of SA that worsened the peroxidization injury to the sensitive C3 plant soybean (Glycine max). The growth inhibition at low concentrations of HSM could be lessened by supplementary BCAAs, reactive oxygen species scavengers or ethylene inducers, whereas the oxidation damage at high concentrations of HSM could not be reversed and ultimately lead to plant death. H2O2 at a low level stimulated the antioxidase system including glutathione S-transferase activities in the HSM-tolerant C4 maize (Zea mays), which contributes to HSM tolerance. H2O2 plays an important role on HSM stress responses in both HSM-sensitive and HSM-tolerant soybean and maize.