Sanguinarine disrupts the colocalization and interaction of HIF-1α with tyrosine and serine phosphorylated-STAT3 in breast cancer

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)-1 alpha. The aim is to investigate the mechanism of HIF-1 alpha 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-1 alpha and STAT3 was analysed in hypoxic TNBC cells and patient samples. The effects of a natural alkaloid, sanguinarine, on HIF-1 alpha and STAT3 colocalization and interaction were evaluated in vitro and mouse xenograft models. We observed strong colocalization of HIF-1 alpha, p-STAT3-Tyr and p-STAT3-Ser in TNBC patient samples. Sanguinarine could inhibit the nuclear colocalization and interaction of HIF-1 alpha with p-STAT3-Tyr and p-STAT3-Ser in vivo and in vitro. Our results may bring insights to the HIF-1 alpha/STAT3 interaction in breast cancers and suggest sanguinarine as a promising candidate for HIF-alpha/STAT3 inhibition.