Y-box-binding proteins (YB proteins) belong to a family of proteins that contain a cold shock domain. The YB protein consists of three members, YB-1, YB-2 and YB-3. Among the YB proteins, YB-1 is the most widely studied one, which plays important roles in DNA repair, cell proliferation and differentiation. Moreover, YB-1 is an oncoprotein that is overexpressed in different types of cancer, including breast cancer. Multiple studies have shown that in stress response, YB-1 is translocated from the cytoplasm to the nucleus and binds to the promoters of its target genes, thereby regulating stemness, multidrug resistance, cell cycle, etc. Furthermore, YB-1 acts primarily as an RNA-binding protein, specifically as a novel RNA 5-methylcytosine reader. It can regulate mRNA transcription, splicing, packaging, stabilization and translation. Additionally, YB-1 promotes the progression of multiple tumor types and serves as a potential tumor biomarker and therapeutic target.
SU056 is a YB-1 inhibitor for cancer research.
SU056 is a YB-1 inhibitor. It induces cell-cycle arrest, and apoptosis, and inhibits cell migration in ovarian cancer cells. Furthermore, it interacts with YB-1 and inhibits its associated downstream proteins and pathways. SU056 can enhance the cytotoxic effects of Paclitaxel. In in vitro studies, SU056 (about 0-10 μM, 48 h) can inhibit the growth of OVCAR3/4/5/8, SKOV3 and ID8 cells. And it inhibits OVCAR-8 and ID8 cell colony formation in a dose-dependent manner, and arrests OVCAR8, SKOV3 and ID8 cells in the sub-G1 phase and G1 phase. In addition, SU056 (0-1 μM for 12 hours) inhibits cell migration and induces apoptosis in OVCAR8, SKOV3 and ID8 cells. Simultaneously, the expression of YB-1, TMSB10, SUMO2 and PMSB2 proteins was suppressed in OVCAR8 cells.
Moreover, In in vivo studies, SU056 (20 mg/kg, intraperitoneal injection) inhibits tumor growth in mice implanted with ID8 cells. SU056 (10 mg/kg, intraperitoneal injection, daily) combined with paclitaxel (HY-B0015) (5 mg/kg, weekly, intraperitoneal injection) inhibited tumor growth in immunodeficient mice implanted with ovarian cancer cells (OVCAR8). Besides, the effect is more obvious than that of administration alone.
In conclusion, SU056 is a YB-1 inhibitor that induces cell cycle arrest, apoptosis and inhibits cell migration of cancer cells.
References:
[1] Dhanir Tailor, et al. Cell Chem Biol. 2021 Aug 19;28(8):1206-1220.e6.
[2] Wiley Interdiscip Rev RNA. 2014 Jan-Feb;5(1):95-110.