z-logo
open-access-imgOpen Access
Phosphosulindac (OXT‐328) Selectively Targets Breast Cancer Stem Cells In Vitro and in Human Breast Cancer Xenografts
Author(s) -
Zhu Caihua,
Cheng KaWing,
Ouyang Nengtai,
Huang Liqun,
Sun Yu,
Constantinides Panayiotis,
Rigas Basil
Publication year - 2012
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.1139
Subject(s) - cancer stem cell , breast cancer , cancer research , wnt signaling pathway , biology , stem cell , cancer , epithelial–mesenchymal transition , signal transduction , metastasis , microbiology and biotechnology , genetics
Abstract Pharmacological targeting of breast cancer stem cells (CSCs) is highly promising for the treatment of breast cancer, as the small population of CSCs appears responsible for tumor initiation and progression and also for resistance to conventional treatment. Here we report that the novel phosphosulindac (OXT‐328, PS) selectively and effectively eliminates breast CSCs both in vitro and in vivo. PS reduced cell proliferation and induced apoptosis in various breast CSCs. Breast CSCs are resistant to conventional cancer drugs but are sensitive to PS. Long‐term treatment of mixtures of cultured breast CSCs and breast cancer cells with PS preferentially eliminated the CSCs. PS impaired the ability of CSCs to form mammospheres and markedly suppressed the expression of CSC‐related genes. More importantly, PS prevented by half ( p =.06) the formation of tumors initiated by CSCs in immunodeficient mice, and inhibited by 83% ( p <.05) the growth of already formed breast cancer xenografts, reducing the proportion of CSCs in them. PS suppressed the Wnt/β‐catenin pathway by stimulating the degradation of β‐catenin and its relocalization to the cell membrane and also blocked the epithelial–mesenchymal transition and the generation of breast CSCs. These results indicate that PS has a strong inhibitory effect against breast cancer, acting, at least in part, by targeting CSCs through a signaling mechanism involving Wnt signaling. S TEM C ells 2012;30:2065–2075

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here