Open AccessChloroquine Eliminates Cancer Stem Cells Through Deregulation of Jak2 and DNMT1
Author(s) -
Choi Dong Soon,
Blanco Elvin,
Kim YooShin,
Rodriguez Angel A.,
Zhao Hong,
Huang Tim HuiMing,
Chen ChunLiang,
Jin Guangxu,
Landis Melissa D.,
Burey Lacey A.,
Qian Wei,
Granados Sergio M.,
Dave Bhuvanesh,
Wong Helen H.,
Ferrari Mauro,
Wong Stephen T. C.,
Chang Jenny C.
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1746
Subject(s) - biology , cancer stem cell , cd44 , cancer research , population , autophagy , side population , chloroquine , cancer cell , stem cell , cancer , pharmacology , immunology , apoptosis , microbiology and biotechnology , cell , medicine , biochemistry , genetics , environmental health , malaria
Triple negative breast cancer (TNBC) is known to contain a high percentage of CD44 + /CD24 −/low cancer stem cells (CSCs), corresponding with a poor prognosis despite systemic chemotherapy. Chloroquine (CQ), an antimalarial drug, is a lysotropic reagent which inhibits autophagy. CQ was identified as a potential CSC inhibitor through in silico gene expression signature analysis of the CD44 + /CD24 −/low CSC population. Autophagy plays a critical role in adaptation to stress conditions in cancer cells, and is related with drug resistance and CSC maintenance. Thus, the objectives of this study were to examine the potential enhanced efficacy arising from addition of CQ to standard chemotherapy (paclitaxel) in TNBC and to identify the mechanism by which CQ eliminates CSCs in TNBCs. Herein, we report that CQ sensitizes TNBC cells to paclitaxel through inhibition of autophagy and reduces the CD44 + /CD24 −/low CSC population in both preclinical and clinical settings. Also, we are the first to report a mechanism by which CQ regulates the CSCs in TNBC through inhibition of the Janus‐activated kinase 2 (Jak2)—signal transducer and activator of transcription 3 signaling pathway by reducing the expression of Jak2 and DNA methyltransferase 1. S tem C ells 2014;32:2309–2323