In our study, three isoforms of 14-3-3 proteins, 14-3-3σ (SFN), 14-3-3β (YWHAB) and 14-3-3ζ (YWHAZ), were enriched in 14-3-3-mediated signaling pathway by IPA analysis, and Western blot analysis demonstrated that the phosphorylation of 14-3-3 in MCF-7 cells and MDA-MB-231 cells was obviously increased after Cos, Dehy, CD or VOSL treatment. c-Jun NH2-terminal kinase (JNK) can antagonize AKT-mediated survival signals by phosphorylating 14-3-3. Research results from Choi et al. revealed that Cos treatment can activate JNK and induce apoptosis in Human Leukemia Cells50. Therefore, we proposed that Cos, Dehy, CD and VOSL treatment all can activate JNK and inactive AKT in breast cancer cells, and then the activated JNK will promote the phosphorylation of 14-3-3, which resulted in releasing the proapoptotic proteins, such as BAD and FOXO, and enhancing the activity of tumor suppressor, such as LKB1, to antagonize AKT-mediated survival signals, and finally to induce cancer cell apoptosis.