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Dose-dependent tuning of HSP70-Beclin-1 by kaempferol governs autophagy and chemosensitivity

Suqin Hu1, Yanan Guo1, Mingyan Li1

  • 1Department of Hepatobiliary Spleen and Stomach, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, China.

Frontiers in Oncology
|June 5, 2026
PubMed
Abstract

Insights

High-dose kaempferol triggers autophagy to enhance chemotherapy effectiveness, while low-dose kaempferol suppresses it. This study reveals how flavonoid dosing controls autophagy directionality and therapeutic outcomes.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Pharmacology

Background:

  • Autophagy's dual role in cell survival and death under therapeutic stress is known.
  • The molecular mechanisms governing autophagy's directionality remain unclear.

Purpose of the Study:

  • To investigate the dose-dependent effects of kaempferol on the HSP70-Beclin-1 complex in esophageal squamous carcinoma.
  • To evaluate kaempferol's impact on chemotherapy-induced autophagy and chemosensitization.

Main Methods:

  • Utilized kaempferol as a model flavonoid in esophageal squamous carcinoma cells.
  • Performed in vitro and in vivo experiments to assess kaempferol's effects on the HSP70-Beclin-1 complex and autophagic flux.
  • Analyzed modulation of AMPK/mTOR and ER stress-JNK signaling pathways.

Main Results:

  • Low-dose kaempferol stabilized the HSP70-Beclin-1 complex, suppressed autophagy, and reduced chemotherapy-induced apoptosis.
  • High-dose kaempferol disrupted the complex, enhanced autophagy via AMPK/mTOR inhibition and ER stress-JNK activation, leading to chemosensitization.
  • In vivo, high-dose kaempferol boosted cisplatin's antitumor activity, while low-dose kaempferol diminished it.

Conclusions:

  • Dose-dependent modulation of the chaperone-autophagy initiation complex dictates autophagy directionality and therapeutic response.
  • Kaempferol's distinct effects highlight a strategy for optimizing natural product dosing for cancer therapy.
  • The findings offer a framework for leveraging autophagy-based chemosensitization in various cancer types.
Keywords:
AMPK/mTOR signalingHSP70–Beclin-1 complexautophagy directionalitydose-dependent regulationkaempferol

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