Identification of Hirsutine as an anti-metastatic phytochemical by targeting NF-ΚB activation

Nuclear factor-ΚB (NF-ΚB) activation has been implicated not only in carcinogenesis but also in cancer cell invasion and metastatic process; therefore, targeting the NF-ΚB pathway is an attractive strategy for controlling metastasis. Amongst 56 chemically defined compounds derived from natural products, we have identified a new phytochemical compound Hirsutine, which strongly suppresses NF-ΚB activity in murine 4T1 breast cancer cells. In accordance with the NF-ΚB inhibition, Hirsutine reduced the metastatic potential of 4T1 cells, as seen in the inhibition of the migration and invasion capacity of 4T1 cells. Hirsutine further inhibited the constitutive expression of MMP-2 and MMP-9 in 4T1 cells, and reduced the in vivo lung metastatic potential of 4T1 cells in the experimental model. Given that the migration of human breast cancer cells was also inhibited, our present study implies that Hirsutine is an attractive phytochemical compound for reducing metastasis potential of cancer cells by regulating tumor-promoting NF-ΚB activity.