A novel small molecule inhibitor of CD151 inhibits proliferation of metastatic triple negative breast cancer cell lines

摘要

The large extracellular loop (LEL) of CD151 is receiving much attention and as such described as a novel potential therapeutic target of metastatic cancers due to presence of functionally important sites. In the present study, three dimensional structure of large extracellular loop of CD151 (LEL) was modeled and validated by RAMPAGE. Virtual screening predicted small molecule inhibitor, NSC 146268 (2-thio-6-azauridine) as potential lead molecule targeting LEL of CD151. The 2-thio-6-azauridine (TAU) presented a specific effect on viability of triple negative breast cancer (TNBC) cell lines, MDA-MB 231 and MDA-MB 468 with IC50 value 6.0 and 6.2 mu g/mL, respectively and least effect on normal breast epithelial cell line (IC50 value 48 mu g/mL). It also exhibited significant anti-proliferative activity comparable to paclitaxel with arrest of cell cycle at G1 phase and induction of apoptosis. PathDIP database predicted cell junction pathways as a possible target of CD151. The protein levels of CD151 together with cell junction scaffold proteins, CD46, E-cadherin, beta-catenin and ZO-1 were decreased with TAU at 50% inhibitory concentration. The present results showcase the CD151 as a potential target together with TAU as possible lead molecule of triple negative breast cancer cell lines.