Colorectal cancer (CRC) is the second common cause of cancer death in the world and its development can be regulated by herbal compounds. Unfortunately, little information is known about the signal pathways of Piper betle isoeugenol in CRC cells (CRCCs). Using three CRC cell lines (SW480, SW620, and HCT116) that represent different molecular characteristics and serve as in vitro models of CRC progression, we found that isoeugenol inhibited cell growth. Wound healing and Boyden chamber assays indicated that isoeugenol inhibited the migration and invasion in CRCCs. Mechanistically, isoeugenol suppressed key regulators of cell cycle progression and epithelial-mesenchymal transition (EMT), including pAKT, CDK4, CDK6, cyclin D1, N-cadherin, and Snail, while increasing the levels of pAMPK, pJNK, pp38 MAPK, and E-cadherin. Cell line-specific modulation of CDK2, cyclin D3, p21, p27, and pERK proteins was also observed. Furthermore, isoeugenol inhibited the enzymatic activities of MMP-2 and MMP-9. Pharmacological inhibition of AMPK or p38 antagonized isoeugenol-suppressed cell growth, migration, invasion, and associated signaling events. In conclusion, these data suggest that isoeugenol may inhibit CRCC growth, migration, and invasion through activations of AMPK and p38 MAPK pathways and modulating pathways involved in cell cycle regulation and EMT.
Liou et al. (Wed,) studied this question.