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image of Ethanolic Extract of Cyperus rotundus Augments Chemosensitivity to Docetaxel and Suppresses Autophagic Flux in HER2-Positive Breast Cancer Cells

Abstract

Introduction

Breast cancer (BC) represents a malignancy affecting populations globally. Its incidence is on the rise. The ethanolic extract of (EECR) has demonstrated potent anticancer activities against multiple human cancer types, inducing apoptosis in BC cells. Autophagic flux protects HER2+ cancer cells from trastuzumab-induced cytotoxicity, so inhibiting it undermines the resistance phenotype. This study aimed to elucidate the therapeutic potential of EECR in trastuzumab-resistant HER2-positive BC and decipher its underlying mechanisms.

Methods

Colony formation assay and Cell Counting Kit-8 (CCK-8) assessed cell viability. Flow cytometry was used for cell cycle analysis and apoptosis detection. Western blotting quantified relevant protein expressions. Nude mice were euthanized prior to tissue harvest. Tumor tissues were excised and processed for histological examination, with 5 μm paraffin sections prepared on glass slides for hematoxylin and eosin (H&E) staining. An orthotopic JIMT-1 cell transplantation tumor model was established, and immunohistochemistry was conducted.

Results

EECR demonstrated a dose-dependent suppressive effect on HER2-positive BC cells, inducing apoptosis and G2-M phase cell cycle arrest. It inhibited autophagic flux, as evidenced by LC3 and p62/SQSTM1 accumulation, and upregulated raptor and phosphorylated Mitogen-Activated Protein Kinase (MAPK) in trastuzumab-resistant JIMT-1 cells. Phosphorylated ERK (pERK)/total ERK and Raptor levels were significantly elevated in EECR-treated JIMT-1 cells compared to other treatment groups. Furthermore, EECR significantly inhibited tumorigenic growth in JIMT-1 cells.

Conclusion

This study reveals that EECR effectively impedes autophagic flux in trastuzumab-resistant HER2-positive breast cancer cells, a mechanism increasingly recognized as central to therapeutic resistance. By promoting LC3B and p62 accumulation and modulating the MAPK/mTOR signaling axis, EECR not only disrupts a key survival pathway in resistant cells but also enhances the efficacy of standard chemotherapeutic agents like docetaxel. These dual effects—autophagy inhibition and chemosensitization—underscore EECR’s therapeutic potential as an adjuvant strategy to overcome trastuzumab resistance. Given its multi-target nature and favorable safety profile, EECR represents a promising candidate for future combination therapy in refractory HER2-positive breast cancer.

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2025-07-21
2025-10-27

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/content/journals/cpb/10.2174/0113892010374529250715164342
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Ethanolic Extract of Cyperus rotundus Augments Chemosensitivity to Docetaxel and Suppresses Autophagic Flux in HER2-Positive Breast Cancer Cells
Bentham Science Publishers ; https://doi.org/10.2174/0113892010374529250715164342
/content/journals/cpb/10.2174/0113892010374529250715164342
/content/journals/cpb/10.2174/0113892010374529250715164342
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  • Article Type:     Research Article
Keywords: ethanolic extract of Cyperus rotundus ; MAPK/mTOR/LC3B pathway ; human epidermal growth factor receptor 2 ; Breast cancer

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