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Oroxin A Induces Autophagic Cell Death in Gastric Cancer Cells Through the MAPK/ERK/REDD1 Axis

Linen Li1, Jianfang Rong1,2, Foqiang Liao1

  • 1Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Cell Biology International
|October 24, 2025
PubMed

Insights

Oroxin A, a natural compound, effectively inhibits gastric cancer growth and migration by triggering programmed cell death through autophagy. This natural flavonoid shows promise for developing novel gastric cancer therapies.

Area of Science:

  • Oncology
  • Natural Product Chemistry
  • Molecular Biology

Background:

  • Gastric cancer (GC) presents a significant global health challenge with limited therapeutic options and high drug resistance.
  • Natural compounds are being investigated for their potential anticancer properties due to multi-target action and low toxicity.
  • Oroxin A (OA) is a flavonoid with potential therapeutic applications.

Purpose of the Study:

  • To investigate the anticancer effects of Oroxin A (OA) on gastric cancer cells.
  • To elucidate the underlying molecular mechanisms of OA's action in gastric cancer.
  • To evaluate OA's therapeutic potential as a natural compound for gastric cancer treatment.

Main Methods:

  • In vitro assays and organoid models were employed to assess OA's impact on cell viability, proliferation, and migration.
  • RNA-sequencing, Western blot, immunofluorescence, and electron microscopy were utilized for mechanistic studies.
  • The role of the MAPK/ERK/REDD1/mTOR signaling pathway in OA-induced cell death was examined.

Main Results:

  • OA demonstrated significant inhibition of gastric cancer cell growth and migration with minimal toxicity to normal gastric cells.
  • OA induced autophagic cell death, distinct from apoptosis, in gastric cancer cells.
  • OA activated the MAPK/ERK pathway, upregulated REDD1, and inhibited mTOR signaling, thereby enhancing autophagy.

Conclusions:

  • Oroxin A triggers autophagic cell death in gastric cancer cells through the MAPK/ERK/REDD1 pathway.
  • OA exhibits potential as a promising natural compound for gastric cancer therapy.
  • Targeting the MAPK/ERK/REDD1 pathway with natural compounds like OA offers a novel therapeutic strategy for gastric cancer.
Keywords:
MAPK/ERKOroxin AREDD1autophagygastric cancer

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