1. Academic Validation
  2. Paeonol attenuates aging MRC-5 cells and inhibits epithelial-mesenchymal transition of premalignant HaCaT cells induced by aging MRC-5 cell-conditioned medium

Paeonol attenuates aging MRC-5 cells and inhibits epithelial-mesenchymal transition of premalignant HaCaT cells induced by aging MRC-5 cell-conditioned medium

  • Mol Cell Biochem. 2018 Feb;439(1-2):117-129. doi: 10.1007/s11010-017-3141-7.
Lihua Yang 1 Shangping Xing 2 Kun Wang 1 Hua Yi 3 Biaoyan Du 4
Affiliations

Affiliations

  • 1 Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
  • 2 School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
  • 3 Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. yihuayi0200@126.com.
  • 4 Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. dubybilll@sohu.com.
Abstract

Senescence-associated secretory phenotype (SASP) factors, such as IL-6 and IL-8, are extremely critical in tissue microenvironment. Senescent human fibroblasts facilitate epithelial-mesenchymal transition (EMT) in premalignant epithelial cells mainly through the secretion of SASP factors. Meanwhile, premalignant human HaCaT Keratinocyte (HaCaT) cells as immortal epithelial cells are susceptible to malignant transformation. Paeonol, an herbal phenolic component found in peonies, exerts Anti-aging and anti-tumor efficacies, while the molecular mechanisms of paeonol on EMT in premalignant HaCaT cells induced by SASP factors are unclear. In this study, we first established a senescent human fetal lung fibroblast MRC-5 cell model using hydrogen peroxide evaluated by senescence-associated β-galactosidase assay. Upon paeonol treatment, intracellular Reactive Oxygen Species levels in aging MRC-5 cells were significantly decreased via regulation of nuclear translocation of Nrf2. Then we curiously studied whether the aging MRC-5 cell-conditioned medium could induce EMT in premalignant HaCaT cells, and the results showed that paeonol significantly reduced the clonogenic, migratory, and invasive capacities of premalignant HaCaT cells potentially induced by IL-6 and IL-8. Moreover, we found that paeonol notably altered pluripotency of EMT-associated markers via the modulation of ERK and TGF-β1/Smad pathway in premalignant HaCaT cells. These findings suggest that paeonol may be used as an Adjuvant therapy for SASP factor-mediated EMT in premalignant lesion.

Keywords

Anti-aging; EMT; HaCaT cells; Malignant transformation; Paeonol; SASP.

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