Panoply™ Human ADAM17 Over-expressing Stable Cell Line

Rosmarinic acid (RA) is a naturally occurring polyphenol compound with various biological properties, including anticancer effects. Metalloproteinase disintegrin and metalloproteinase 17 (ADAM17) can activate epidermal growth factor receptor (EGFR) ligands and promote tumor progression. Here, researchers investigated whether RA exerts its anticancer effects in melanoma cells by downregulating ADAM17. The results showed that compared to normal cells, RA treatment significantly reduced cell viability, proliferation, migration, and invasion capabilities, melanin content, and the expression of related proteins, including MMP2 and MMP9, in A375 cells. RA increased the proportion of TUNEL-positive cells and the expression of pro-apoptotic proteins, but decreased Bcl-2 expression. RA combined with cisplatin (Cis) treatment enhanced the inhibitory effect of cisplatin on cell viability. RA inhibited the expression of the ADAM17/EGFR/AKT/GSK3β signaling pathway, and the ADAM17 inhibitor (TACE prodomain; TPD) further enhanced this inhibition. Furthermore, ADAM17 overexpression blocked all effects of RA, while TPD treatment produced the opposite effect. In conclusion, RA significantly inhibits the proliferation, migration, and invasion of melanoma cells, but promotes apoptosis.

To verify our hypothesis that RA can downregulate ADAM17 expression and inhibit the EGFR/AKT signaling pathway, thereby suppressing melanoma progression, researchers overexpressed ADAM17 in A375 cells (Figures 1a and 1b). Figure 1c shows that cell proliferation was significantly increased in ADAM17-overexpressing cells, but after combined treatment with TPD in the presence of RA, cell proliferation was significantly reduced, even lower than in cells treated with RA alone. Compared to RA treatment, the migration and invasion abilities of ADAM17-overexpressing cells were also increased, while TPD reduced these cellular functions. Therefore, it can be concluded that ADAM17 overexpression can block, while TPD can enhance, the inhibitory effect of RA on cell migration and invasion (Figures 1d-g). These results indicate that the expression of MMP2 and MMP9, which were inhibited by RA in A375 cells, was significantly restored after ADAM17 overexpression and further reduced after combined treatment with TPD.

Figure 1. ADAM17 overexpression reverses, whereas ADAM17 inhibition enhances the effect of RA on melanoma cells proliferation, migration and invasion. (Huang L, et al., 2021)