Breast cancer is one leading cause of death in females, especially triple-negative breast cancer (TNBC). Hypoxia is a key feature leading to tumour progression driven by hypoxia-inducible factor (HIF)-1α. The aim is to investigate the mechanism of HIF-1α and signal transducer and activator of transcription-3 (STAT3) interaction and discover a compound to disrupt the interaction in breast cancer cells. The regulation pattern of HIF-1α and STAT3 was analysed in hypoxic TNBC cells and patient samples. The effects of a natural alkaloid, sanguinarine, on HIF-1α and STAT3 colocalization and interaction were evaluated in vitro and mouse xenograft models. We observed strong colocalization of HIF-1α, p-STAT3-Tyr and p-STAT3-Ser in TNBC patient samples. Sanguinarine could inhibit the nuclear colocalization and interaction of HIF-1α with p-STAT3-Tyr and p-STAT3-Ser in vivo and in vitro. Our results may bring insights to the HIF-1α/STAT3 interaction in breast cancers and suggest sanguinarine as a promising candidate for HIF-α/STAT3 inhibition.
Keywords: Breast cancer; Hypoxia-inducible factor-1α; Sanguinarine; Signal transducer and activator of transcription-3.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.