Cytotoxic diterpenoids from the roots of Euphorbia jolkinii Boiss against human pancreatic cancer SW1990 cells by regulating the expressions of Bcl-2, Bax, and Caspase-3 proteins

Sixteen undescribed diterpenoids were identified from Euphorbia jolkinii Boiss, a widespread invasive plant in the grassland ecosystem of subalpine meadows in southwest China, through a combination of spectroscopic data analysis. These included two casbane diterpenoids ( 1 and 2 ), two ent -atisane diterpenoids ( 3 and 4 ), and twelve ent -isopimarane diterpenoids ( 5 – 16 ). All isolates were evaluated the cytotoxicity on pancreatic cancer SW1990 cells in which compounds 1 and 9 exhibited obvious bioactivities against the tumor cells with the IC 50 values of 26.50 ± 6.36 and 21.09 ± 5.98 μM respectively. Moreover, compounds 1 and 9 were found to promote the pre-apoptosis of SW1990 cells and regulate the expressions of Bcl-2, Bax, and Caspase-3 proteins to display anti-tumor abilities. Compounds 1 and 9 were subjected to Bcl-2 protein via molecular ducking to reveal their anti-tumor mechanism further. The druggability prediction showed that they possessed good drug properties with development and utilization scenarios.