Discovery of Highly Oxidized Abietane Diterpenoids from the Roots of Euphorbia fischeriana with Anti-tumor Activities

Main observation and conclusion Four previously undescribed ent-abietane diterpenoids (1-4), along with twelve known analogues (5-16), were isolated from the roots of wild Euphorbia fischeriana. Their gross structures were determined via extensive spectroscopic data, and the absolute configurations were elucidated by means of single-crystal X-ray diffraction analysis, Rh-2(OCOCF3)(4)-induced CD spectrum and ECD calculations. Their cervical carcinoma inhibition activities counteract HeLa cells were screened by MTT assay, and the structure-activity relationships were further examined. The results demonstrated that 2 (IC50 value at 3.75 mu mol/L) was more potent than cisplatin. The underlying mechanism study revealed that 2 could distinctly induce apoptosis accompanied by increasing reactive oxygen species (ROS) production, Ca2+ influx and decreasing mitochondrial membrane potential. Furthermore, signal pathways including MAPKs/AKT might play a significant role in 2-induced cervical cancer cells death.