Angelic acid

Angelic acid is a ferroptosis inducer, targeting NRF2 degradation. Angelic acid binds to NRF2 protein and promotes NRF2 degradation via ubiquitination-proteasome pathway, relieves the inhibitory effect of NRF2 on oxidative stress and lipid peroxidation. Then, Angelic acid induces ferroptosis in tumor cells. Angelic acid can enhance the accumulation of intracellular reactive oxygen species (ROS), upregulate ferroptosis-related markers CHAC1 and PTGS2, and synergize with ferroptosis inducers to enhance anti-tumor effects. Angelic acid also has the activity of scavenging UVA-induced ROS in vitro, inhibiting skin fibroblast senescence and extracellular matrix degradation. Angelic Acid helps wound healing with sedative activity^[1][2]. In Vitro: Angelic acid (200 μM; 24 h) synergistically inhibits the cell viability and cell proliferation of DLD1 and SW480 colorectal cancer cells with RSL3 (2 μM)^[1].
Angelic acid (200 μM; 24 h) upregulates the mRNA expression of ferroptosis-related genes CHAC1 and PTGS2 in DLD1 cells, reduces the protein level of NRF2, and increases K48 ubiquitination modification^[1].
Angelic acid (5-15 μM; 6 h pretreatment + UVA irradiation) significantly reduces the level of intracellular reactive oxygen species induced by UVA in the ROS detection experiment of normal human dermal fibroblasts (NHDFs), restores the GSH content, and upregulates the gene expression of antioxidant enzymes such as GPx1, SOD1/2, and CAT^[2].
In Vivo: Angelic acid (8 mg/kg; intraperitoneal injection; once every 2 days; 20 days) synergistically inhibits tumor growth in the CT26 colorectal cancer subcutaneous xenograft model in Balb/c mice^[1].