Luteolin exhibits anti-breast cancer property through up-regulating miR-203

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3265-3271. doi: 10.1080/21691401.2019.1646749.

Abstract

Luteolin is a representative of natural flavonoid that has anti-tumour properties. This study designed to check its impact on breast cancer and the underlying mechanisms. MDA-MB-453 and MCF-7 cells were administrated with luteolin and the following techniques were carried out: CCK-8 assay, FITC-PI double-staining and Western blot. qRT-PCR analysis was utilized to see the effects of luteolin on miR-203 expression. Besides, miR-203 expression was silenced by transfection with specific inhibitor. Luteolin remarkably declined MDA-MB-453 and MCF-7 cells viability and accelerated apoptosis which accompanied by Bax up-regulation, Bcl-2 down-regulation and Caspase-3 cleavage. Also, luteolin impeded TGFβ1-induced EMT, as evidenced by the decreased levels of Vimentin, Zeb1 and N-cadherin, as well as the increased level of E-cadherin. miR-203 was highly expressed in 22 pair of breast cancer tissues than the matched paracancerous tissues. Luteolin could elevate miR-203 level. Besides, luteolin's anti-tumour effects were partially eliminated by miR-203 silence. Further, luteolin inhibited Ras/Raf/MEK/ERK signalling, while the inhibitory effects were flattened by miR-203 silence. Luteolin significantly reduced breast cancer cells growth and EMT. Luteolin exerted its anti-tumour effects possibly involved the elevated expression of miR-203 and the inhibited Ras/Raf/MEK/ERK signalling.

Keywords: MCF-7 cell; MDA-MB-453 cell; Ras/Raf/MEK/ERK signalling; apoptosis; epithelial-mesenchymal transition (EMT).

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / pathology*
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Luteolin / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • raf Kinases / metabolism
  • ras Proteins / metabolism

Substances

  • Antineoplastic Agents
  • MIRN203 microRNA, human
  • MicroRNAs
  • raf Kinases
  • ras Proteins
  • Luteolin