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Andrographolide Induces Noxa-Dependent Apoptosis by Transactivating ATF4 in Human Lung Adenocarcinoma Cells

Junqian Zhang1, Chunjie Li1, Li Zhang1

  • 1Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Frontiers in Pharmacology
|May 17, 2021
PubMed

Insights

Andrographolide (AD) inhibits lung adenocarcinoma cell growth. This traditional Chinese medicine component induces apoptosis by activating the ATF4/Noxa pathway, offering a promising new chemotherapy candidate.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Lung adenocarcinoma presents poor patient outcomes, necessitating novel therapeutic strategies.
  • Andrographolide (AD), from traditional Chinese medicine, shows potential antitumor activity but its role in lung adenocarcinoma is unclear.

Purpose of the Study:

  • To investigate the therapeutic potential and underlying mechanism of Andrographolide (AD) in lung adenocarcinoma.

Main Methods:

  • Assessed AD's effect on lung cancer cell proliferation.
  • Investigated AD-induced apoptosis and the role of Noxa and ATF4 using cell lines (A549, H1299) and siRNA knockdown.

Main Results:

  • AD inhibited lung cancer cell proliferation dose-dependently.
  • High-dose AD induced Noxa-dependent apoptosis, mediated by ATF4 transcriptional activation of Noxa.
  • ATF4 knockdown reduced Noxa transactivation and AD-induced apoptosis.

Conclusions:

  • AD induces apoptosis in human lung adenocarcinoma cells via the ATF4/Noxa axis.
  • AD demonstrates potential as a novel chemotherapeutic agent for lung adenocarcinoma.
Keywords:
ATF4TCMandrographolideapoptosislung adenocarcinomanoxa

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