Our previous researches revealed that Cos and Dehy in VOSL exhibited synergistic anti-breast cancer efficiency both in vitro and in vivo. In this study, we tried to investigate their molecular mechanisms. Increased proliferation capacities, uncontrolled cell cycle progression and apoptosis inhibition are the hallmark of cancer. Accordingly, the agents targeting one or more of these processes should be ideal cancer chemopreventive candidates5. Our research results demonstrated that VOSL, sesquiterpene lactones-rich fraction, can inhibit MCF-7 cell proliferation, induce cell cycle arrest and promote apoptosis through c-Myc/p53 signaling pathway and AKT/14-3-3 signaling pathway.