Breast cancer suppression by aplysin is associated with inhibition of PI3K/AKT/FOXO3a pathway

Xinling Zhang1, Tingting Zhuang2, Zhengyan Liang1

  • 1The Institute of Human Nutrition, Medical College of Qingdao University, Qingdao 266021, China.

Oncotarget
|October 4, 2017
PubMed

Insights

Aplysin, a compound from Aplysia kurodai, inhibits breast cancer growth by down-regulating the PI3K/AKT/FOXO3a pathway, promoting apoptosis and suggesting its potential as a chemoprevention drug.

Area of Science:

  • Marine Natural Products
  • Cancer Biology
  • Molecular Pharmacology

Background:

  • Aplysin, a bromosesquiterpene from Aplysia kurodai, shows potential anti-cancer properties.
  • The precise mechanisms of aplysin's anti-cancer effects, particularly against breast cancer, are not fully understood.

Purpose of the Study:

  • To investigate the anti-breast cancer mechanisms of aplysin.
  • To explore the role of the PI3K/AKT/FOXO3a signaling pathway in aplysin's effects.

Main Methods:

  • In vivo tumor growth suppression assays.
  • In vitro cell proliferation and apoptosis assays.
  • Western blot analysis to assess protein phosphorylation and expression levels of key pathway and apoptosis-related genes.
  • Gene silencing using shRNA and pathway activation using an activator.

Main Results:

  • Aplysin significantly suppressed tumor growth in vivo and inhibited proliferation while promoting apoptosis in vitro.
  • Aplysin down-regulated the PI3K/AKT/FOXO3a pathway by reducing phosphorylation of AKT and FOXO3a.
  • Aplysin altered the expression of FOXO3a target genes, decreasing cyclin D1 and Bcl-XL, and increasing p21CIP1, p27KIP1, Bim, TRAIL, and FasL.
  • Pharmacological activation of PI3K/AKT or silencing of FOXO3a conferred resistance to aplysin's anti-cancer effects.

Conclusions:

  • Aplysin suppresses breast cancer progression by inhibiting the PI3K/AKT/FOXO3a signaling pathway.
  • These findings highlight aplysin's potential as a chemopreventive agent for breast cancer.

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