14-Deoxycoleon U-induced endoplasmic reticulum stress-mediated apoptosis, autophagy, and cell cycle arrest in lung

Xiaozhi Peng1, Yijun Tu1, San Fu2

  • 1Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Department of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, 430065, People's Republic of China.

Oncotargets and Therapy
|September 20, 2019
PubMed
Abstract

Insights

14-Deoxycoleon U effectively inhibits lung adenocarcinoma cell proliferation by inducing apoptosis, endoplasmic reticulum stress, and autophagy. This natural compound shows promise for treating lung cancer in vitro and in vivo.

Area of Science:

  • Pharmacology
  • Cancer Biology
  • Molecular Biology

Background:

  • 14-Deoxycoleon U is a natural abietane-type diterpene with demonstrated inhibitory effects on tumor cell proliferation.
  • Lung adenocarcinoma is a significant global health concern, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To evaluate the potential of 14-Deoxycoleon U as a therapeutic agent for lung adenocarcinoma.
  • To investigate the in vitro and in vivo efficacy of 14-Deoxycoleon U against lung adenocarcinoma.

Main Methods:

  • Cell viability and apoptosis were assessed using cell counting kit-8 assay and Hoechst 33258 staining.
  • Western blot analysis was employed to measure protein expression related to apoptosis, ER stress, autophagy, and cell cycle.
  • Autophagosome formation was visualized via confocal microscopy, and an in vivo LLC lung adenocarcinoma model was established.

Main Results:

  • 14-Deoxycoleon U significantly inhibited A549 and LLC cell proliferation in a dose-dependent manner, inducing caspase-dependent apoptosis.
  • Apoptosis was mediated by 14-Deoxycoleon U-induced endoplasmic reticulum stress and promoted by autophagy.
  • Cell cycle arrest was observed, linked to modulation of key cell cycle regulatory proteins.

Conclusions:

  • 14-Deoxycoleon U demonstrates significant anti-cancer activity against lung adenocarcinoma both in vitro and in vivo.
  • The compound's efficacy is attributed to ER stress-mediated apoptosis, autophagy, and cell cycle arrest.
  • 14-Deoxycoleon U presents a promising lead compound for lung cancer treatment with potentially lower adverse effects than adriamycin.