title: Verapamil preferentially potentiates in-vitro cytotoxicity of vincristine on malignant lymphoid cells.
abstract: Verapamil has been shown to overcome acquired drug resistance to vincristine in P388 leukemia both in vitro and in vivo. To study the selectivity of this action, the effect of addition of verapamil on the cytotoxicity of vincristine was studied using lymphocytes from eight patients with chronic lymphocytic leukemia (CLL), lymphoblasts from a T-acute lymphoblastic leukemia (T-ALL) cell line (GM 3639), and peripheral blood lymphocytes (PBL) from eight normal healthy volunteers. Using the differential staining cytotoxicity (DiSC) assay, we demonstrated that verapamil at 1 microM concentration potentiated the in-vitro cytotoxicity of vincristine on CLL and GM 3639 cells in concentrations of 0.04-0.25 micrograms/l. There was however, no enhancement of cytotoxicity noted against the control PBL. The data demonstrate that verapamil preferentially enhances the in-vitro cytotoxicity of vincristine on CLL and GM 3639 cells but no enhancement of cytotoxicity is seen against PBL.
authors.affiliation: Aga Khan University Hospital, Karachi, Pakistan.
authors.forename: I A
authors.initials: IA
authors.lastname: Malik
authors.forename: N V
authors.initials: NV
authors.lastname: Costea
mesh_terms: D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use*; D014750:Vincristine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014750:Vincristine; D014700:Verapamil