PT  - JOURNAL ARTICLE
AU  - Hortelano, Sonsoles
AU  - Boscá, Lisardo
TI  - 6-Mercaptopurine Decreases the Bcl-2/Bax Ratio and Induces Apoptosis in Activated Splenic B Lymphocytes
DP  - 1997 Mar 01
TA  - Molecular Pharmacology
PG  - 414--421
VI  - 51
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/51/3/414.short
4100  - http://molpharm.aspetjournals.org/content/51/3/414.full
SO  - Mol Pharmacol1997 Mar 01; 51
AB  - 6-Mercaptopurine and related purine antimetabolites are used in the treatment of several B cell disorders. These drugs inhibited the proliferation of mature splenic B cells after being triggered with polyclonal mitogens. In addition to the antiproliferative effects, 6-mercaptopurine, 2-mercaptopurine, and aminoguanidine evoked a rapid apoptotic cell death in activated B cells that started at 6 hr after drug treatment and therefore preceded DNA synthesis. Incubation of activated B lymphocytes with 6-mercaptopurine blocked the low but sustained nitric oxide release observed in these cells that contributes to the prevention of apoptotic cell death; the addition of chemical nitric oxide donors significantly antagonized the apoptosis elicited by these drugs. The inhibition of nitric oxide synthesis elicited by mercaptopurines correlated with a decrease in the release of nitric oxide-derived species to the culture medium and in the intracellular levels of cGMP. The ratio between the amounts of Bcl-2 and Bax, two proteins involved in the control of apoptosis in mature B cells, markedly decreased as result of mercaptopurine treatment. The American Society for Pharmacology and Experimental Therapeutics