The activity of methylated and non-methylated selenium species in lymphoma cell lines and primary tumours.
BACKGROUND
Diffuse large B-cell lymphoma patients with low serum selenium concentration at presentation have a lower response rate and overall survival than patients with higher serum selenium. The co-administration of selenium with conventional chemotherapy may be useful in these patients.


METHODS
We investigated the activity of two selenium species, methylseleninic acid (MSA) and selenodiglutathione (SDG) in a panel of human lymphoma cell lines and in a primary lymphoma culture system.


RESULTS
Both compounds demonstrated cytostatic and cytotoxic activity with EC(50) values in the range 1.0-10.2 microM. Cell death was associated with an increase in the sub-G1 (apoptotic) fraction by flow cytometry and was not preceded by any obvious cell cycle arrest. SDG, but not MSA, resulted in marked increases in intracellular ROS, particularly in CRL2261 and SUD4 cells in which the cytotoxic activity of SDG was partly, or completely, inhibited by n-acetyl cysteine, suggesting a dependence on ROS for activity in some cells. Both MSA and SDG showed a concentration dependent reduction in percentage viability after a 2-day exposure in primary lymphoma cultures, with EC(50) values in the range 39-300 microM and 9-28 microM, respectively.


CONCLUSIONS
The selenium compounds MSA and SDG induce cell death in lymphoma cell lines and primary lymphoma cultures, which with SDG may be partly attributable to the generation of ROS.
Cancer Research UK Medical Oncology Unit, St Bartholomew's Hospital, London, UK.
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Last
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Maharaj
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Perry
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Strauss
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Fitzgibbon
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TA
Lister
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S
Joel
D017209:Apoptosis / Q000187:drug effects*; D002908:Chronic Disease; D005434:Flow Cytometry; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D016393:Lymphoma, B-Cell / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D008745:Methylation; D016566:Organoselenium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016566:Organoselenium Compounds; C017710:selenodiglutathione; C008493:methylselenic acid; D005978:Glutathione