Pachymic acid promotes induction of autophagy related to IGF-1 signaling pathway in WI-38 cells

Phytomedicine. 2017 Dec 1:36:82-87. doi: 10.1016/j.phymed.2017.09.020. Epub 2017 Sep 29.

Abstract

Background: The insulin-like growth factor 1 (IGF-1) signaling pathway has spotlighted as a mechanism to elucidate aging associated with autophagy in recent years. Therefore, we have tried to screen an effective compound capable of inducing autophagy to delay aging process.

Purpose: The aim of this study is to investigate whether pachymic acid, a main compound in Poria cocos, induces autophagy in the aged cells.

Methods: The aging of young cells was induced by treatment with IGF-1 at 50 ng/ml three times every two days. The effect of pachymic acid on cell viability was evaluated in human lung fibroblasts, WI-38 cells, using MTT assay. The induction of autophagy was detected using autophagy detection kit. The expression of proteins related to autophagy and IGF-1 signaling pathway was examined by western blot analysis and immunofluorescence assay.

Results: In this study, pachymic acid showed cytotoxic effect in a dose dependent manner and remarkably induced autophagy at the same time. Moreover, pachymic acid increased the expression of proteins related to autophagy such as LC3-II and Beclin1 and decreased the levels of mTor phosphorylation and p70S6K in the aged cells. In particular, pachymic acid increased the expression of p-PI3K, p-FoxO and Catalase. In addition, pachymic acid remarkably increased the expression of IGFBP-3.

Conclusion: Above results suggest that pachymic acid could induce autophagy related to IGF-1 signaling pathway in the aged cells.

Keywords: Autophagy; FoxO; IGF-1; IGFBP-3; Pachymic acid; Poria cocos.

MeSH terms

  • Autophagy / drug effects*
  • Autophagy / physiology
  • Cell Line
  • Cell Survival / drug effects
  • Cellular Senescence / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor I / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Triterpenes / pharmacology*

Substances

  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Triterpenes
  • Insulin-Like Growth Factor I
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • pachymic acid