Loading...
PLGA-nano-encapsulated disulfiram inhibits cancer stem cells and targets non-small cell lung cancer in vitro and in vivo
Butcher, Kate Wang, Zhipeng Kurusamy, Sathishkumar Zhang, Zaixing Najlah, Mohammad McConville, Christopher Kannappan, Vinodh
Butcher, Kate
Wang, Zhipeng
Kurusamy, Sathishkumar
Zhang, Zaixing
Najlah, Mohammad
McConville, Christopher
Kannappan, Vinodh
Editors
Other contributors
Epub Date
Issue Date
2024-12-23
Submitted date
Alternative
Abstract
Cancer stem cells (CSCs) play a key role in non-small cell lung cancer (NSCLC) chemoresistance and metastasis. In this study, we used two NSCLC cell lines to investigate the regulating effect of hypoxia in the induction and maintenance of CSC traits. Our study demonstrated hypoxia-induced stemness and chemoresistance at levels comparable to those in typical CSC sphere culture. Activation of the NF-κB pathway (by transfection of NF-κB-p65) plays a key role in NSCLC CSCs and chemoresistance. Disulfiram (DS), an anti-alcoholism drug, showed a strong in vitro anti-CSC effect. It blocked cancer cell sphere reformation and clonogenicity, synergistically enhanced the cytotoxicity of four anti-NSCLC drugs (doxorubicin, gemcitabine, oxaliplatin and paclitaxel) and reversed hypoxia-induced resistance. The effect of DS on CSCs is copper-dependent. A very short half-life in the bloodstream is the major limitation for the translation of DS into a cancer treatment. Our team previously developed a poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated DS (DS-PLGA) with a long half-life in the bloodstream. Intra venous injection of DS-PLGA in combination with the oral application of copper gluconate has strong anticancer efficacy in a metastatic NSCLC mouse model. Further study may be able to translate DS-PLGA into cancer applications.
Citation
Butcher K, Wang Z, Kurusamy S, Zhang Z, Morris MR, Najlah M, McConville C, Kannappan V, Wang W. PLGA-Nano-Encapsulated Disulfiram Inhibits Cancer Stem Cells and Targets Non-Small Cell Lung Cancer In Vitro and In Vivo. Biomolecules. 2024; 14(12):1651. https://doi.org/10.3390/biom14121651
Publisher
Journal
Research Unit
PubMed ID
39766358 (pubmed)
PubMed Central ID
Embedded videos
Additional Links
Type
Journal article
Language
en
Description
© 2025 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/biom14121651
Series/Report no.
ISSN
2218-273X
EISSN
2218-273X
ISBN
ISMN
Gov't Doc #
Sponsors
The grant (RG14-8) was awarded to WW and CM by British Lung Foundation. VK was the Postdoctoral Fellow supported by the grant.