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01-01-2021 | Breast Cancer | Original Article

Galeterone sensitizes breast cancer to chemotherapy via targeting MNK/eIF4E and β-catenin

Authors: Yulin Xu, Shichong Liao, Lijun Wang, Yuan Wang, Wen Wei, Ke Su, Yi Tu, Shan Zhu

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2021

Abstract

Aberrant activation of eIF4E signalling pathway is common in breast cancer and holds potential therapeutic options. In our work, galeterone as a chemical compound under clinical trials for the treatment of prostate cancer, was identified to be effective in targeting breast cancer cells via suppressing MNK-eIF4E and β-catenin. In despite of varying IC50, galeterone at nanomolar concentrations significantly decreased viability, proliferation and migration of a panel of breast cancer cell lines regardless of clinical subtypes and genetic mutations, and to a higher extent than in normal breast cells. Galeterone significantly enhanced the effects of chemotherapeutic drugs in reducing proliferation and viability but not migration. The in vivo efficacy of galeterone as single drug alone and its ability in augmenting chemotherapy’s efficacy were also shown in breast cancer xenograft mouse model. Mechanism analysis demonstrated that galeterone decreased MNK1/2 level and phosphorylation of eIF4E. In addition, galeterone decreased β-catenin level via promoting GSK-3β-mediated β-catenin degradation, and furthermore that Akt but not CK1 was involved in β-catenin degradation by galeterone. Rescue studies demonstrated that both MNK/eIF4E and β-catenin were responsible for anti-breast cancer activity of galeterone. Our study provides pre-clinical evidence to initialize clinical trials for breast cancer using galeterone in combination with chemotherapy.

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Title: Galeterone sensitizes breast cancer to chemotherapy via targeting MNK/eIF4E and β-catenin
Authors: Yulin Xu
Shichong Liao
Lijun Wang
Yuan Wang
Wen Wei
Ke Su
Yi Tu
Shan Zhu
Publication date: 01-01-2021
Publisher: Springer Berlin Heidelberg
Keywords: Breast Cancer
Breast Cancer
Cytostatic Therapy
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2021
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04195-w

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