Niclosamide reverses adipocyte induced epithelial-mesenchymal transition in breast cancer cells via suppression of the interleukin-6/STAT3 signalling axis

Scientific Reports
Jones GyamfiJunjeong Choi

Abstract

The microenvironment of breast cancer comprises predominantly of adipocytes. Adipocytes drive cancer progression through the secretion adipocytokines. Adipocytes induce epithelial mesenchymal transition of breast cancer cells through paracrine IL-6/Stat3 signalling. Treatment approaches that can target adipocytes in the microenvironment and abrogate paracrine signals that drive breast cancer growth and metastasis are urgently needed. Repositioning of old drugs has become an effective approach for discovering new cancer drugs. In this study, niclosamide, an FDA approved anthelminthic drug was evaluated for its anti-breast cancer activity and its ability to inhibit adipocytes induced EMT. Niclosamide potently inhibited proliferation, migration and invasion at low concentration and induced significant apoptosis at high concentrations in human breast cancer cell lines MDA-MB-468 and MCF-7. Additionally, niclosamide reversed adipocyte-induced EMT with a correlated inhibition of IL-6/Stat3 activation and downregulation of EMT-TFs TWIST and SNAIL. Moreover, niclosamide markedly impaired MDA-MB-468 and MCF-7 migration and invasion. We further found that the inhibitory effects of niclosamide on MDA-MB-468 and MCF-7 motility was closely ...Continue Reading

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Citations

Aug 14, 2020·Journal of Experimental & Clinical Cancer Research : CR·Chongru ZhaoYiping Wu
Jul 28, 2020·Journal of Cancer Research and Clinical Oncology·Hyeong-Cheol OhSeok-Gu Kang
Dec 15, 2020·World Journal of Stem Cells·Xu Gao, Qiong-Zhu Dong
Feb 11, 2021·Cancers·Damiano Cosimo RigiraccioloRosamaria Lappano
Mar 31, 2021·Molecular Metabolism·Riya ShresthaFrances L Byrne
May 12, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Jingshan CaiShengjun Wang
Jun 4, 2021·BMC Complementary Medicine and Therapies·Seth A DomfehMohamed Mutocheluh
Oct 23, 2021·Molecular Medicine Reports·Huihui Yao, Songbing He

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Methods Mentioned

BETA
flow cytometry
PCR
co-immunoprecipitation assay
transfection

Software Mentioned

GraphPad Prism
ImageJ

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