Yang_2023_Cell.Signal_105_110610

Loliolide (LL), a naturally occurring monoterpenoid lactone isolated from Vicia tenuifolia Roth, can exhibit numerous pharmacological effects such as those related to anti-Parkinson, anti-oxidant, anti-cholinesterase, and anti-depressant. Epithelial-mesenchymal transition (EMT) plays a pivotal role in regulating tumor metastasis. CXCR4 and CXCR7 are G-protein-coupled receptors (GPRs), which can be stimulated by CXCL12. CXCL12/CXCR4/CXCXR7 axis can cause activation of multiple pathways including MAPKs, JAK/STAT pathway, and manganese superoxide dismutase (MnSOD) signaling. These events can initiate EMT process and induce cell invasion and migration. Here, we investigated whether LL can modulate the CXCR4 and CXCR7 and EMT process in colon cancer and breast cancer cells. We found that LL suppressed levels of CXCR4 and CXCR7, and exerted an inhibitory effect on these chemokines even after stimulation by CXCL12. LL suppressed expression of MnSOD and mesenchymal markers, whereas induced epithelial markers. In addition, LL significantly attenuated cellular invasion, migration, and metastasis. We noted that LL inhibited CXCR4/7 and EMT process even after stimulation of CXCL12 and MnSOD overexpression. Therefore, in this study, we provide evidences that targeting CXCR4/7 and MnSOD could inhibit the invasion, migration, and metastasis of cancer cells as well as negatively regulate the EMT process. Overall, our study suggested that LL might act as a potent suppressor of EMT process against colon and breast cancer cells.