To investigate the dose-dependent effects of kaempferol on the HSP70–Beclin-1 complex and its implications for autophagy and chemotherapy response in esophageal squamous carcinoma cells, highlighting its potential therapeutic significance.
Key Findings:
Low-dose kaempferol stabilizes the HSP70–Beclin-1 complex, suppressing autophagy and reducing chemotherapy-induced apoptosis through specific signaling pathways.
High-dose kaempferol disrupts the HSP70–Beclin-1 complex, enhancing autophagic flux and promoting chemosensitization via AMPK/mTOR inhibition and ER stress–JNK signaling.
In vivo, high-dose kaempferol enhances the antitumor activity of cisplatin, while low-dose kaempferol diminishes it, indicating a critical dose-dependent effect.
Interpretation:
The study identifies a dose-dependent mechanism by which kaempferol modulates autophagy through the HSP70–Beclin-1 interaction, influencing cancer cell responses to chemotherapy, with implications for optimizing treatment strategies.
Limitations:
The study primarily focuses on esophageal squamous carcinoma cells, limiting generalizability to other cancer types; further studies are needed to explore kaempferol's effects in different cancer models.
Further in vivo studies are needed to confirm the clinical relevance of the findings, particularly in human subjects.
Conclusion:
Kaempferol's modulation of the HSP70–Beclin-1 complex presents a potential strategy for optimizing autophagy-based chemosensitization in cancer therapy, warranting further investigation into its clinical applications.
