STM2457 Inhibits Breast Cancer Tumorigenesis via the Inhibition of METTL3

Abstract

Although N 6 -adenosine methyltransferase (METTL3) is frequently upregulated in breast cancer patients, the anticancer effect of small-molecule inhibitors targeting METTL3 has not yet been studied. The present study aimed to investigate the anti-tumorigenic effects of STM2457, a METTL3 inhibitor, on a panel of breast cancer cells representing distinct clinical subtypes. Measurement of cell viability using MTT assay demonstrated dose-and time-dependent reduction in viability in MCF7, SKBR3, and MDA-MB-231 cells, which are representative of luminal A, HER2-positive, and triple-negative breast cancer subtypes, respectively. Immunoblotting analysis revealed that STM2457 induced pro-apoptotic effects in breast cancer cells, as evidenced by the cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3. In addition, analysis of cell cycle distribution with flow cytometry revealed that it induced cell cycle arrest at G0/G1-phase. Consistently, treatment with STM2457 increased the Annexin V-stained cell population, corroborating the pro-apoptotic effects of the compound. Moreover, analysis of colonies formed by breast cancer cells in a soft agar matrix showed that STM2457 reduced the anchorage-independent growth of breast cancer cells, suggesting its potential to inhibit colony formation. Together, these findings indicate that STM2457 exerts cytotoxic and pro-apoptotic effects in breast cancer cells. Our study demonstrates the therapeutic potential of METTL3 inhibitor STM2457 in treating breast cancer patients.