Anti‑metastatic effects of arctigenin are regulated by MAPK/AP‑1 signaling in 4T‑1 mouse breast cancer cells.
Mol Med Rep. 2020 Mar ;21(3):1374-1382. Epub 2020 Jan 13. PMID: 32016480
Arctigenin is a natural lignan that is found in burdock with anti‑viral, ‑oxidative, ‑inflammatory and anti‑tumor activities. In the current study, the effect of arctigenin on metastatic potential was examined in 4T‑1 mouse triple‑negative breast cancer cells. The results indicated that arctigenin inhibited cell motility and invasiveness, which was determined using wound healing and transwell invasion assays. Arctigenin suppressed matrix metalloprotease‑9 (MMP‑9) activity via gelatin zymography, and protein expression of cyclooxygenase‑2 (COX‑2) and MMP‑3. Furthermore, arctigenin attenuated the mRNA expression of metastatic factors,including MMP‑9, MMP‑3 and COX‑2. Based on these results, the effect of arctigenin on the mitogen‑activated protein kinase (MAPK)/activating protein‑1 (AP‑1) signaling pathway was assessed in an attempt to identify the regulatory mechanism responsible for its anti‑metastatic effects.Arctigenin was demonstrated to inhibit the phosphorylation of extracellular signal‑regulated protein kinase (ERK) and c‑Jun N‑terminal kinase (JNK), and the nuclear translocations of the AP‑1 subunits, c‑Jun and c‑Fos. In summary, the present study demonstrated that in 4T‑1 mouse triple‑negative breast cancer cells the anti‑metastatic effect of arctigenin is mediated by the inhibition of MMP‑9 activity and by the inhibition of the metastasis‑enhancing factors MMP‑9, MMP‑3 and COX‑2, due to the suppression of the MAPK/AP‑1 signaling pathway. The results of the current study demonstrated that arctigenin exhibits a potential for preventing cell migration and invasion in triple negative breast cancer.