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

J Cell Mol Med. 2020 Aug;24(15):8430-8440. doi: 10.1111/jcmm.15371. Epub 2020 Jun 20.

Abstract

Alpinetin, the main active ingredient in the Chinese medicinal herb Alpinia 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-1α (HIF-1α) signalling due to a lack of NF-κB activation through reduced mitochondrial reactive oxygen species (ROS) production, decreasing HIF-1α transcription. In vivo, we also found alpinetin led to significant tumour regression by inhibiting NF-κB pathway. Overall, our work uncovers a ROS/NF-κB/HIF-1α axis-dependent mechanism underlying the anticancer effects of alpinetin and suggests that alpinetin could act as a novel therapeutic agent against breast cancer.

Keywords: HIF-1α; NF-κB; ROS; alpinetin; apoptosis; breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Cell Proliferation / drug effects*
  • Female
  • Flavanones / pharmacology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NF-kappa B / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects*
  • Transcription, Genetic / drug effects

Substances

  • Flavanones
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • NF-kappa B
  • Reactive Oxygen Species
  • alpinetin