Verapamil inhibits B-cell proliferation and tumor necrosis factor release and induces a clinical response in B-cell chronic lymphocytic leukemia.
Four B-CLL patients, treated with verapamil for cardiac problems, showed substantial reduction of lymphadenopathy in one, a 3- and 5-year stabilization of B-CLL in two patients, and a dramatic decrease in lymphocyte count, lymphadenopathy and splenomegaly in one stage IV patient. We therefore studied the effects of verapamil on B-CLL cells in vitro. In 13 samples we observed that verapamil strongly inhibited in vitro proliferation of pokeweed mitogen (PWM) stimulated and unstimulated cells. Using a cytotoxic bioassay, we found that verapamil markedly inhibited the spontaneous and PMW-induced release of tumor necrosis factor (TNF) by B-CLL cells. These findings suggest that verapamil may block B-CLL cell proliferation through inhibition of TNF release and thereby may contribute to the management of B-CLL.
Berrebi
A
A
Hematology Institute, Kaplan Hospital, Rehovot, Israel.
Shtalrid
M
M
Klepfish
A
A
Bassous
L
L
Kushnir
M
M
Shulman
L
L
Vorst
E
E
Hahn
T
T
D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use*
D014409:Tumor Necrosis Factor-alpha; D014700:Verapamil; D002118:Calcium