The novel Jab1 inhibitor CSN5i-3 suppresses cell proliferation and induces apoptosis in human breast cancer cells

Hua Xiao, Francois-Xavier Claret,  Qian Shen

Abstract:

Jab1 is a vital subunit of the CSN family and is reported to be overexpressed in numerous cancer types. Due to the importance of Jab1/CSN5 in cancer cell proliferation and survival, Jab1 is considered a promising therapeutic target. Therefore, we evaluated the anticancer effect of the novel Jab1 inhibitor CSN5i-3 in breast cancer cells. In our study, we found that Jab1 was overexpressed in breast cancer tissues and was correlated with poor prognosis in human breast cancer patients. An MTS assay revealed that CSN5i-3 suppressed cell proliferation in the breast cancer cell lines BT474 and SKBR3. We also found that CSN5i-3 significantly induced apoptosis and G1 phase cell cycle arrest in breast cancer cells. A mechanistic investigation revealed that CSN5i-3 inhibited Jab1 expression and increased the level of the apoptosis marker cleaved PARP and the cell-cycle-related protein p27 in BT474 and SKBR3 cells. A nude mouse xenograft model also indicated that CSN5i-3 exerted a potent anticancer effect in vivo. Overall, our study suggested that the Jab1 inhibitor CSN5i-3 might be a promising agent for the treatment of breast cancer in humans and should be studied further.