Breast cancer stem cell selectivity of synthetic nanomolar-active salinomycin analogs

BMC Cancer
Xiaoli HuangStina Oredsson

Abstract

Cancer stem cells (CSCs) have been invoked in resistance, recurrence and metastasis of cancer. Consequently, curative cancer treatments may be contingent on CSC selective approaches. Of particular interest in this respect is the ionophore salinomycin, a natural product shown to be 100-fold more active against CSCs than clinically used paclitaxel. We have previously reported that synthetic salinomycin derivatives display increased activity against breast cancer cell lines. Herein we specifically investigate the CSC selectivity of the most active member in each class of C20-O-acylated analogs as well as a C1-methyl ester analog incapable of charge-neutral metal ion transport. JIMT-1 breast cancer cells were treated with three C20-O-acylated analogs, the C1-methyl ester of salinomycin, and salinomycin. The effects of treatment on the CSC-related CD44(+)/CD24(-) and the aldehyde dehydrogenase positive (ALDH(+)) populations were determined using flow cytometry. The survival ability of CSCs after treatment was investigated with a colony formation assay under serum free conditions. The effect of the compounds on cell migration was evaluated using wound-healing and Boyden chamber assays. The expression of vimentin, related to mesenchym...Continue Reading

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Citations

Jun 22, 2016·ACS Medicinal Chemistry Letters·Björn BorgströmDaniel Strand
Jul 20, 2016·Cancers·Kamal AhmedVladimir L Katanaev
Feb 15, 2019·PloS One·Johannes KloseMartin Schneider
Aug 4, 2016·The Oncologist·Maximilian BoeschDominik Wolf
Nov 5, 2019·Frontiers in Oncology·Sangita SridharanDayanidhi Raman
Nov 9, 2018·Stem Cells International·Petra GenerSimó Schwartz
Jan 6, 2019·European Journal of Medicinal Chemistry·Michał Antoszczak
Jan 29, 2019·Journal of the American Chemical Society·Fengfei WangErxi Wu
May 18, 2020·Clinical Breast Cancer·Nupur Mukherjee, Chinmay Kumar Panda
Apr 16, 2021·Toxicology Reports·Atena Malakpour-Permlid, Stina Oredsson
Jun 16, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Alicja UrbaniakAngus M MacNicol
Jul 6, 2018·ACS Central Science·Xiaoli HuangDaniel Strand

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Methods Mentioned

BETA
chemical modifications
flow cytometry
FCS

Software Mentioned

GraphPad Prism
ImageJ

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