Evaluation of 6-mercaptopurine in a cell culture model of adaptable triple-negative breast cancer with metastatic potential.

Evaluation of 6-mercaptopurine in a cell culture model of adaptable triple-negative breast cancer with metastatic potential. Oncotarget. 2019 Jun 04;10(38):3681-3693 Authors: Singh B, Sarli VN, Kinne HE, Shamsnia A, Lucci A Abstract Progenitor-like cancer cells that can survive in reversible quiescence when faced with various challenges in the body are often behind disease progression. A lack of glutamine in culture medium, which eliminates >99.9% of proliferating SUM149 triple-negative breast cancer cells, selects such adaptable, pan-resistant cells. Our data support the hypothesis that a lack of glutamine forces the selection of an epigenetic state that does not require a high level of TET2, thus selecting an "undifferentiated" therapy-resistant phenotype as seen in TET2-mutant cancers. Our data suggesting that highly adaptable cells are generated through reprograming of the epigenome and transcriptome led us to evaluate low-dose 6-mercaptopurine as a potential therapy in our model. We found that a long treatment with low-dose 6-mercaptopurine inhibited the proliferation of these adaptable cells to a greater extent than it inhibited parental cells. Importantly, a small percentage of adaptable cells survived a low-dose 6-mercaptopurine treatment in a reversible quiescence, analogous to the persistence of abnormal progenitor-like cells in inflammatory bowel disease, which stays in a durable remission with a 6-mercaptopurine treatm...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research