Delphinidin suppresses breast carcinogenesis through the HOTAIR/microRNA-34a axis

Bin Han1, Xiaoli Peng1, Daomei Cheng1

  • 1School of Public Health, Chengdu Medical College, Chengdu, China.

Cancer Science
|July 21, 2019
PubMed

Insights

Delphinidin, a plant compound, effectively suppresses breast cancer in rats by regulating the HOTAIR/microRNA-34a pathway. This natural compound shows promise for preventing breast carcinogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Natural Products Chemistry

Background:

  • Anthocyanidins, like delphinidin, exhibit significant anti-cancer properties.
  • Breast cancer remains a leading cause of mortality, necessitating novel therapeutic strategies.
  • Understanding molecular mechanisms underlying cancer development is crucial for prevention and treatment.

Purpose of the Study:

  • To investigate the anti-cancer effects of delphinidin on 1-methyl-1-nitrosourea (MNU)-induced breast carcinogenesis in rats.
  • To elucidate the molecular mechanism involving the HOTAIR/microRNA-34a axis in delphinidin's action.
  • To evaluate delphinidin's impact on key signaling pathways implicated in breast cancer progression.

Main Methods:

  • MNU-induced rat breast cancer model.
  • Delphinidin administration and assessment of tumor suppression.
  • Analysis of HOTAIR and microRNA-34a expression levels.
  • Western blot analysis for Wnt/β-catenin pathway proteins (β-catenin, Gsk3β, c-Myc, cyclin-D1) and MMP-7.
  • RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays.

Main Results:

  • Delphinidin significantly suppressed MNU-induced breast carcinogenesis in rats.
  • Delphinidin downregulated HOTAIR and upregulated microRNA-34a expression.
  • Delphinidin reduced the expression of β-catenin, Gsk3β, c-Myc, cyclin-D1, and MMP-7.
  • MicroRNA-34a inhibition diminished delphinidin's effects on c-Myc, cyclin-D1, and MMP-7.
  • HOTAIR overexpression counteracted delphinidin's effects on microRNA-34a and the Wnt/β-catenin pathway.
  • Delphinidin enhanced EZH2 and H3K27me3, indicating epigenetic regulation of HOTAIR/microRNA-34a.

Conclusions:

  • Delphinidin demonstrates potent anti-cancer activity against breast carcinogenesis.
  • The anti-cancer mechanism involves negative regulation of the HOTAIR/microRNA-34a axis.
  • Delphinidin's action is linked to the modulation of the Wnt/β-catenin signaling pathway.
  • These findings support delphinidin's potential as a preventive agent for breast cancer.

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