In vitro testing of calcium channel blockers and cytotoxic chemotherapy in B-cell low-grade non-Hodgkin's lymphoma.
The flux of calcium forms an important intracellular messenger system. The bcl-2 oncoprotein is thought to make cells resistant to a variety of insults, including cytotoxic drugs, by the suppression of apoptosis, which appears to involve the repartitioning of intracellular calcium. Three drugs that affect calcium pathways and may influence this repartitioning, i.e. dantrolene, azumolene (a water-soluble dantrolene analogue) and nimodipine, were studied in cell culture, using both a transformed follicle centre lymphoma cell line and primary culture of lymphoma cells in vitro in a manner that resulted in a growth pattern closely resembling that of the malignancy in vivo. Dantrolene and azumolene were potent inducers of cell death in both systems reducing the viable cell count by 70-90% in comparison with normal controls. Nimodipine, in comparison, appeared to have no significant effect. These results obtained in an in vitro setting suggest that further evaluation of dantrolene and azumolene for the treatment of low-grade non-Hodgkin's lymphoma is warranted.
Shamash
J
J
ICRF Department of Medical Oncology, St Bartholomew's Hospital, London, UK.
Salam
A H
AH
Davies
D C
DC
Williams
A
A
Joel
S
S
Lister
T A
TA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D016923:Cell Death; D002455:Cell Division; D002461:Cell Line, Transformed; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D015870:Gene Expression; D019254:Genes, bcl-2; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008214:Lymphocytes; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics; D009553:Nimodipine / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D011241:Prednisone / Q000008:administration & dosage / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D007093:Imidazoles; D010080:Oxazoles; D009553:Nimodipine; D014750:Vincristine; C061387:azumolene; D004317:Doxorubicin; D003520:Cyclophosphamide; D003620:Dantrolene; D011241:Prednisone