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Full-Text Articles in Oncology
Alterations In Glutathione Levels And Apoptotic Regulators Are Associated With Acquisition Of Arsenic Trioxide Resistance In Multiple Myeloma, Shannon M. Matulis, Alejo A. Morales, Lucy Yehiayan, Kelvin P. Lee, Yong Cai, Lawrence H. Boise
Alterations In Glutathione Levels And Apoptotic Regulators Are Associated With Acquisition Of Arsenic Trioxide Resistance In Multiple Myeloma, Shannon M. Matulis, Alejo A. Morales, Lucy Yehiayan, Kelvin P. Lee, Yong Cai, Lawrence H. Boise
Department of Chemistry and Biochemistry
Arsenic trioxide (ATO) has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2–3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH) …