The anticancer properties and mechanism of action of tablysin-15, the RGD-containing disintegrin, in breast cancer cells

Abstract α v β 3 integrin expressed on cancer cell surfaces is associated with important cancer hallmarks including survival and metastasis and is thus a potential anticancer drug target. Tablysin-15 contains the RGD motif and is a high-affinity α v β 3 integrin antagonist. The aim of this study was to investigate the antitumor effect and mechanism of action of tablysin-15 against α v β 3 integrin high-expressing breast cancer cell lines in vitro and in vivo . Tablysin-15 dose-dependently inhibited the proliferation, migration, and invasion of two breast cancer cell lines via the α v β 3 integrin in vitro . Proliferation inhibition was attributable to G0/G1 phase cell cycle arrest rather than apoptosis or necrosis. Furthermore, tablysin-15 downregulated the activity and mRNA expression of MMP-2/-9, VEGF, and COX-2 but upregulated TIMP-1/-2 mRNA in both cell lines. Further, tablysin-15 suppressed the expression of CDK2, CDK6, cyclin D1, and cyclin E, the phosphorylation of FAK, Akt, GSK-3β, and ERK, and the nuclear translocation of NF-κB while increasing the expression of the CDK inhibitor p21 waf1/C1 . Lastly, tablysin-15 provided effective antitumor protection in vivo . Thus, tablysin-15 inhibits the metastasis and proliferation of breast cancer cells through binding α v β 3 integrin and blocking FAK-associated signaling pathways as well as nuclear translocation of NF-κB.