Bufalin attenuates triple-negative breast cancer cell stemness by inhibiting the expression of SOX2/OCT4.

Triple-negative breast cancer (TNBC) has the poorest prognosis among all types of breast cancer and there is yet no effective therapy. Chemotherapy is the traditional standard of care for patients with TNBC; however, treatment of TNBC with chemotherapy may lead to the enrichment of cancer stem cells (CSCs), which exhibitan enhanced capacity for self-renewal, tumor initiation and metastasis. The present study demonstrated that bufalin, a small molecular compound used in traditional Chinese medicine, exerted anticancer effects on a wide range of cancer cell lines, inhibited cell proliferation through inducing G2/M cell cycle arrest, and triggered apoptosis in the TNBC cell lines MDA-MB-231 and HCC-1937. Consistently, bufalin markedly suppressed TNBC growth in a cell line-derived xenograft model. More importantly, unlike common chemotherapeutic drugs, bufalin reduced the stemness of TNBC stem cells. A mechanistic study suggested that bufalin may suppress the proliferation of TNBC stem cells by inhibiting the expression of octamer-binding transcription factor 4 (OCT4) and sex determining region Y-box 2 (SOX2) in MDA-MB-231 and HCC-1937 cells. These results indicated that bufalin may hold promise as a therapeutic agent in TNBC, and its effects may be mediated through the SOX2/OCT4 axis.