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2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione mediates the effect of ROS-enhanced PI3K/Akt/mTOR pathway on

Linqian Chen1, Meifeng Chen2, Yan Xie1

  • 1Guangxi Medical University School of Pharmacy, Nanning, China.

FEBS Open Bio
|December 9, 2024
PubMed

Insights

The compound 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) inhibits breast cancer cell proliferation and tumor growth. DMDD enhances autophagy and apoptosis by affecting the PI3K/Akt/mTOR pathway and increasing reactive oxygen species (ROS).

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) has shown potential antitumor effects.
  • The precise mechanism of DMDD's action, particularly its impact on key signaling pathways, requires further elucidation.

Purpose of the Study:

  • To investigate the effect of DMDD on the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway in breast cancer.
  • To understand the role of reactive oxygen species (ROS), apoptosis, and autophagy in DMDD's antitumor activity.

Main Methods:

  • In vitro studies using breast cancer cell lines (MDA-MB-231 and MCF-7) treated with DMDD.
  • In vivo studies using a mouse breast cancer xenograft model treated with DMDD.
  • Analysis of PI3K/Akt/mTOR pathway components (mRNA and protein), ROS levels, apoptosis markers, and autophagy markers (LC3II/I, p62).

Main Results:

  • DMDD significantly inhibited the proliferation of MDA-MB-231 and MCF-7 breast cancer cells.
  • DMDD treatment increased intracellular ROS levels, apoptosis, and autophagy.
  • DMDD downregulated PI3K, Akt, and mTOR expression while upregulating LC3II/I and p62 proteins.
  • In vivo, DMDD inhibited tumor growth, with increased ROS and apoptotic cells observed in treated tumors.

Conclusions:

  • DMDD exhibits antitumor effects in breast cancer by inhibiting cell proliferation and tumor growth.
  • DMDD's mechanism involves enhancing autophagy and apoptosis, potentially mediated by increased ROS production.
  • The PI3K/Akt/mTOR signaling pathway is implicated in DMDD's effects on breast cancer, suggesting a novel therapeutic strategy.
Keywords:
2‐dodecyl‐6‐methoxycyclohexa‐2,5‐diene‐1,4‐dionePI3K/Akt/mTOR signaling pathwayROSautophagybreast cancer

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