Selenite is a potent cytotoxic agent for human primary AML cells.
Selenite is a potent inhibitor of malignant cell growth. Although the cytotoxic effects have been extensively investigated in vitro, there are only a limited number of studies using primary tumor cells with concomitant comparison to conventional drugs. An ex vivo model with primary cells from 39 consecutive patients with acute myeloid leukemia (AML) were exposed to a panel of conventional cytotoxic drugs, and the effects on viability were compared to those of clinically achievable concentrations of selenite. Selenite at 5 microM caused the lowest mean survival of primary tumor cells in the panel of all tested drugs (28.95% CI 18.60-39.30%). The cells showed a significant (p<0.05) correlation in the resistance to all tested conventional AML drugs whereas selenite did not, indicating sensitivity to selenite also in multi drug resistant cells. Exposure to selenite also resulted in an increased mRNA expression of the antioxidant proteins TrxR1 and Grx, while staining for TrxR1 showed decreased protein levels. The results strongly suggest a great potential for selenite in the treatment of multi drug resistant AML.
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge F46, Stockholm, Sweden.
Eric
E
Olm
Kerstin
K
Jönsson-Videsäter
Inmaculada
I
Ribera-Cortada
Aristi P
AP
Fernandes
Lennart C
LC
Eriksson
Sören
S
Lehmann
Anna-Klara
AK
Rundlöf
Christer
C
Paul
Mikael
M
Björnstedt
D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018038:Sodium Selenite / Q000494:pharmacology*
D003603:Cytotoxins; D000255:Adenosine Triphosphate; D018038:Sodium Selenite