Daphnane diterpenoids for cancer therapy by suppressing ATR-mediated DNA damage response pathway

In this study, 26 structurally diverse daphnane diterpenoids (1-26) including six undescribed ones (1-6) were isolated from the whole plants of Daphne odora. Compounds 1 and 2 were the most active with IC50 values of 3.57 ± 0.32 and 4.35 ± 0.14 µM, respectively. Mechanistic study indicated that 1 and 2 could significantly induce cell cycle arrest at the G2/M phase and cause cell apoptosis. Further examination by transcriptome sequencing analysis revealed that 1 and 2 significantly suppressed ATR-mediated DNA damage response and cell cycle checkpoint. Overall design: HCC827 non-small cell lung cancer cells mRNA profiles of treatment with compounds 1 and 2 (5 µM, 24h)