Much evidence indicates that the α,β-unsaturated carbonyl group in the α-methylene-γ-butyrolactone (Fig. 1) moiety of Cos and Dehy may play crucial roles through conjugation with SH-groups of target proteins to exert various biological activities, such as anti-inflammatory, anti-cancer, anti-virus, anti-oxidant, anti-diabetes, anti-ulcer, and anthelmintic activities, etc.5, of which, the anti-cancer activities and associated molecular mechanisms of Cos or Dehy have been reported in recent years, including inhibiting cancer cell proliferation6, accelerating apoptosis7, inducing cancer cell differentiation8, inhibiting metastasis and invasion9, reversing multidrug resistance10, restraining angiogenesis11. Our previous studies had demonstrated that VOSL has better anti-breast cancer efficacy and lower side effects than Cos or Dehy in vivo3, however, to the best of our knowledge, the synergistic anti-cancer molecular mechanism of Cos and Dehy (CD) in VOSL has not yet been studied.