Isobavachalcone sensitizes cells to E2-induced paclitaxel resistance by down-regulating CD44 expression in ER+ breast cancer cells

Junfeng Shi; Yi Chen; Wenxing Chen; Cuiju Tang; Honghong Zhang; Yuetong Chen; Xiuwei Yang; Zhi Xu; Jingsun Wei; Jinfei Chen

doi:10.1111/jcmm.13719

Isobavachalcone sensitizes cells to E2-induced paclitaxel resistance by down-regulating CD44 expression in ER+ breast cancer cells

Junfeng Shi, Yi Chen, Wenxing Chen, Cuiju Tang, Honghong Zhang, Yuetong Chen, Xiuwei Yang, Zhi Xu, Jingsun Wei, Jinfei Chen

Pharmacology and Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Oestrogen receptor (ER) is expressed in approximately 60%-70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER-positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER-negative (ER−) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β-estradiol (E₂)-induced paclitaxel resistance and that E₂ could stimulate CD44 expression in ER+ breast cancer cells but not in ER− cells. Meanwhile, E₂ could promote ERα expression to render ER+ breast cancer cells resistant to paclitaxel. Furthermore, we established paclitaxel-resistant breast cancer cell lines and determined the function of ERα in the enhancement of paclitaxel resistance via the regulation of CD44 transcription. IBC down-regulated ERα and CD44 expression and thus inhibited tumour growth in paclitaxel-resistant xenograft models. Overall, our data demonstrated for the first time that IBC could decrease CD44 expression level via the ERα pathway and make ER+ breast cancer cells sensitive to paclitaxel treatment.

Original language	English
Pages (from-to)	5220-5230
Number of pages	11
Journal	Journal of Cellular and Molecular Medicine
Volume	22
Issue number	11
DOIs	https://doi.org/10.1111/jcmm.13719
State	Published - Nov 2018

Bibliographical note

Publisher Copyright:
© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Funding

the project of Science & Technology of Nanjing, Grant/Award Number: YKK14081; the Natural Science Foundation of Jiangsu Province, Grant/Award Number: BK20150092; the National Natural Science Foundation of China, Grant/Award Number: 81502623; the Key R & D Special Fund of Jiangsu Province, Grant/Award Number: BE2017611

Funders	Funder number
Key R & D Special Fund of Jiangsu Province	BE2017611
Nanjing University of Information Science & Technology	YKK14081
National Natural Science Foundation of China (NSFC)	81502623
Natural Science Foundation of Jiangsu Province	BK20150092

Keywords

CD44
breast cancer
isobavachalcone
oestrogen receptor alpha
paclitaxel resistance

ASJC Scopus subject areas

Molecular Medicine
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/jcmm.13719

Cite this

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title = "Isobavachalcone sensitizes cells to E2-induced paclitaxel resistance by down-regulating CD44 expression in ER+ breast cancer cells",

abstract = "Oestrogen receptor (ER) is expressed in approximately 60%-70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER-positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER-negative (ER−) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β-estradiol (E2)-induced paclitaxel resistance and that E2 could stimulate CD44 expression in ER+ breast cancer cells but not in ER− cells. Meanwhile, E2 could promote ERα expression to render ER+ breast cancer cells resistant to paclitaxel. Furthermore, we established paclitaxel-resistant breast cancer cell lines and determined the function of ERα in the enhancement of paclitaxel resistance via the regulation of CD44 transcription. IBC down-regulated ERα and CD44 expression and thus inhibited tumour growth in paclitaxel-resistant xenograft models. Overall, our data demonstrated for the first time that IBC could decrease CD44 expression level via the ERα pathway and make ER+ breast cancer cells sensitive to paclitaxel treatment.",

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author = "Junfeng Shi and Yi Chen and Wenxing Chen and Cuiju Tang and Honghong Zhang and Yuetong Chen and Xiuwei Yang and Zhi Xu and Jingsun Wei and Jinfei Chen",

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AU - Shi, Junfeng

AU - Chen, Yi

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AU - Tang, Cuiju

AU - Zhang, Honghong

AU - Chen, Yuetong

AU - Yang, Xiuwei

AU - Xu, Zhi

AU - Wei, Jingsun

AU - Chen, Jinfei

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AB - Oestrogen receptor (ER) is expressed in approximately 60%-70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER-positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER-negative (ER−) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β-estradiol (E2)-induced paclitaxel resistance and that E2 could stimulate CD44 expression in ER+ breast cancer cells but not in ER− cells. Meanwhile, E2 could promote ERα expression to render ER+ breast cancer cells resistant to paclitaxel. Furthermore, we established paclitaxel-resistant breast cancer cell lines and determined the function of ERα in the enhancement of paclitaxel resistance via the regulation of CD44 transcription. IBC down-regulated ERα and CD44 expression and thus inhibited tumour growth in paclitaxel-resistant xenograft models. Overall, our data demonstrated for the first time that IBC could decrease CD44 expression level via the ERα pathway and make ER+ breast cancer cells sensitive to paclitaxel treatment.

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Isobavachalcone sensitizes cells to E2-induced paclitaxel resistance by down-regulating CD44 expression in ER+ breast cancer cells

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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