Induction of immunogenic cell death in radiation-resistant breast cancer stem cells by repurposing anti-alcoholism drug disulfiram.

Cell Communication and Signaling : CCS
Ting SunXinhui Wang

Abstract

The current successful clinical use of agents promoting robust anti-tumor immunity in cancer patients warrants noting that radiation therapy (RT) induces immunogenic cell death (ICD) of tumor cells, which can generate anti-tumor immune responses. However, breast cancer stem cells (BCSCs) are resistant to RT and RT alone usually failed to mount an anti-tumor immune response. High aldehyde dehydrogenase activity (ALDH)bright and CD44+/CD24-/ESA+ cancer cells, previously shown to have BCSC properties, were isolated from human MDA-MB-231 and UACC-812 breast cancer cell lines by flow cytometer. Flow sorted BCSCs and non-BCSCs were further tested for their characteristic of stemness by mammosphere formation assay. Induction of ICD in BCSCs vs. non-BCSCs in response to different in vitro treatments was determined by assessing cell apoptosis and a panel of damage-associated molecular pattern molecules (DAMPs) by flow and enzyme-linked immunosorbent assay (ELISA). We found that ionizing radiation (IR) triggered a lower level of ICD in BCSCs than non-BCSCs. We then investigated the ability of disulfiram/cooper (DSF/Cu) which is known to preferentially induce cancer stem cells (CSCs) apoptosis to enhance IR-induced ICD of BCSCs. The resul...Continue Reading

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Citations

Oct 30, 2020·OncoTargets and Therapy·Rui WangJun Zhou
Dec 15, 2020·World Journal of Stem Cells·Xu Gao, Qiong-Zhu Dong
Sep 10, 2020·Biology of Reproduction·Sneh M Toprani, Varsha Kelkar Mane
Jan 12, 2021·Cancer Chemotherapy and Pharmacology·Chen LuXiao Zhang
Feb 25, 2021·Hematology/oncology and Stem Cell Therapy·Sneh M Toprani, Varsha Kelkar Mane
Jul 25, 2021·Cancers·Francisco D Rodriguez, Rafael Coveñas

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Methods Mentioned

BETA
flow cytometry
reverse transcription PCR
Assay
ELISA
FACS
flow

Software Mentioned

SPSS
FlowJo
ALDEFLUOR

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