TY - JOUR
T1 - Glutathione may have implications in the design of 3-bromopyruvate treatment protocols for both fungal and algal infections as well as multiple myeloma
AU - Niedzwiecka, Katarzyna
AU - Dylag, Mariusz
AU - Augustyniak, Daria
AU - Majkowska-Skrobek, Grazyna
AU - Cal-Bakowska, Magdalena
AU - Ko, Young H.
AU - Pedersen, Peter L.
AU - Goffeau, Andre
AU - Ulaszewski, Stanislaw
PY - 2016
Y1 - 2016
N2 - In different fungal and algal species, the intracellular concentration of reduced glutathione (GSH) correlates closely with their susceptibility to killing by the small molecule alkylating agent 3-bromopyruvate (3BP). Additionally, in the case of Cryptococcus neoformans cells 3BP exhibits a synergistic effect with buthionine sulfoximine (BSO), a known GSH depletion agent. This effect was observed when 3BP and BSO were used together at concentrations respectively of 4-5 and almost 8 times lower than their Minimal Inhibitory Concentration (MIC). Finally, at different concentrations of 3BP (equal to the half-MIC, MIC and double-MIC in a case of fungi, 1 mM and 2.5 mM for microalgae and 25, 50, 100 μM for human multiple myeloma (MM) cells), a significant decrease in GSH concentration is observed inside microorganisms as well as tumor cells. In contrast to the GSH concentration decrease, the presence of 3BP at concentrations corresponding to sub-MIC values or half maximal inhibitory concentration (IC50) clearly results in increasing the expression of genes encoding enzymes involved in the synthesis of GSH in Cryptococcus neoformans and MM cells. Moreover, as shown for the first time in the MM cell model, the drastic decrease in the ATP level and GSH concentration and the increase in the amount of ROS caused by 3BP ultimately results in cell death.
AB - In different fungal and algal species, the intracellular concentration of reduced glutathione (GSH) correlates closely with their susceptibility to killing by the small molecule alkylating agent 3-bromopyruvate (3BP). Additionally, in the case of Cryptococcus neoformans cells 3BP exhibits a synergistic effect with buthionine sulfoximine (BSO), a known GSH depletion agent. This effect was observed when 3BP and BSO were used together at concentrations respectively of 4-5 and almost 8 times lower than their Minimal Inhibitory Concentration (MIC). Finally, at different concentrations of 3BP (equal to the half-MIC, MIC and double-MIC in a case of fungi, 1 mM and 2.5 mM for microalgae and 25, 50, 100 μM for human multiple myeloma (MM) cells), a significant decrease in GSH concentration is observed inside microorganisms as well as tumor cells. In contrast to the GSH concentration decrease, the presence of 3BP at concentrations corresponding to sub-MIC values or half maximal inhibitory concentration (IC50) clearly results in increasing the expression of genes encoding enzymes involved in the synthesis of GSH in Cryptococcus neoformans and MM cells. Moreover, as shown for the first time in the MM cell model, the drastic decrease in the ATP level and GSH concentration and the increase in the amount of ROS caused by 3BP ultimately results in cell death.
KW - 3-bromopyruvate (3BP)
KW - Buthionine sulfoximine
KW - Fungi
KW - Genes expression
KW - Glutathione
KW - MM cells
UR - http://www.scopus.com/inward/record.url?scp=84994182406&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994182406&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.11592
DO - 10.18632/oncotarget.11592
M3 - Article
C2 - 27582536
AN - SCOPUS:84994182406
SN - 1949-2553
VL - 7
SP - 65614
EP - 65626
JO - Oncotarget
JF - Oncotarget
IS - 40
ER -