Alpinetin inhibits breast cancer growth by ROS/NF-κB/HIF-1α axis

Alpinetin, the main active ingredient in the Chinese medicinal herbAlpinia katsumadai Hayata, has been found to have anticancer activity. However, the therapeutic efficacy of signalling cascades modulated by alpinetin remains unknown. Here, we showed that alpinetin provoked mitochondria-associated apoptosis in a dose-dependent manner in breast cancer cells. Mechanistic investigations revealed that alpinetin dampens hypoxia-inducible factor-1 alpha (HIF-1 alpha) signalling due to a lack of NF-kappa B activation through reduced mitochondrial reactive oxygen species (ROS) production, decreasing HIF-1 alpha transcription. In vivo, we also found alpinetin led to significant tumour regression by inhibiting NF-kappa B pathway. Overall, our work uncovers a ROS/NF-kappa B/HIF-1 alpha axis-dependent mechanism underlying the anticancer effects of alpinetin and suggests that alpinetin could act as a novel therapeutic agent against breast cancer.