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Cancer Chemotherapy and Pharmacology

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01-05-2021 | Breast Cancer | Original Article

Honokiol antagonizes doxorubicin resistance in human breast cancer via miR-188-5p/FBXW7/c-Myc pathway

Authors: Xianglan Yi, Liping Lou, Jun Wang, Jing Xiong, Sheng Zhou

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2021

Abstract

Background

Honokiol, a natural phenolic compound derived from Magnolia plants, is a promising anti-tumor compound that exerts a wide range of anti-cancer effects. Herein, we investigated the effect of honokiol on doxorubicin resistance in breast cancer.

Methods

Doxorubicin-sensitive (MCF-7 and MDA-MB-231) and doxorubicin-resistant (MCF-7/ADR and MDA-MB-231/ADR) breast cancer cell lines were treated with doxorubicin in the absence or presence of honokiol; then, the following tests were performed: flow cytometry for cell apoptosis, WST-1 assay for cell viability, qPCR and western blot for the expression of miR-188-5p, FBXW7, and c-Myc. MiR-188-5p mimic, miR-188-5p inhibitor, siFBXW7, and c-Myc plasmids were transfected into cancer cells to evaluate whether miR-188-5p and FBXW7/c-Myc signaling are involved in the effect of honokiol on doxorubicin resistance in breast cancer. A dual luciferase reporter system was used to study the direct interaction between miR-188-5p and FBXW7.

Results

Honokiol sensitized doxorubicin-resistant breast cancer cells to doxorubicin-induced apoptosis. Mechanically, upregulation of miR-188-5p was associated with doxorubicin resistance, and honokiol enhanced doxorubicin sensitivity by downregulating miR-188-5p. FBXW7 was confirmed to be a direct target gene of miR-188-5p. FBXW7/c-Myc signaling was involved in the chemosensitization effect of honokiol. Honokiol induced apoptosis in MCF-7/ADR and MDA-MB-231/ADR cells. However, FBXW7 silencing or c-Myc transfection resulted in resistance to the honokiol-induced apoptotic effect.

Conclusion

These findings suggest that downregulation of miR-188-5p by honokiol enhances doxorubicin sensitivity through FBXW7/c-Myc signaling in human breast cancer. Our study finds an important role of miR-188-5p in the development of doxorubicin resistance in breast cancer, and enriches our understanding of the mechanism of action of honokiol in cancer therapy.

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Title: Honokiol antagonizes doxorubicin resistance in human breast cancer via miR-188-5p/FBXW7/c-Myc pathway
Authors: Xianglan Yi
Liping Lou
Jun Wang
Jing Xiong
Sheng Zhou
Publication date: 01-05-2021
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Breast Cancer
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2021
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-021-04238-w

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Abstract

Background

Methods

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