In vitro activity of vinorelbine on human leukemia cells.
Vinorelbine (VNR) is a semi-synthetic Vinca rosea alkaloid that has been employed both as a single agent and in combination, and has shown significant antitumor activity. As little is known about VNR activity on human leukemia, we studied its in vitro cytotoxic effect on human leukemia cell lines (FLG 29.1, HL60, K562, Balm 4, CEM and Daudi) and on fresh leukemia cells from 28 patients: 2 acute myeloid leukemia (AML); 3 chronic myeloid leukemia in blastic phase (CML-BP); 5 acute lymphoblastic leukemia (ALL); 18 B-chronic lymphatic leukemia (B-CLL), employing the colorimetric INT assay and determining the IC50. We observed that VNR exerts its cytotoxic activity on leukemic cell lines in a dose-dependent fashion. The lymphoid cell lines appear more sensitive than the myeloid ones to the VNR-dependent growth inhibition. A similar pattern was noticed for leukemia cells in primary cultures. VNR is not effective on CML-BP cells, shows variable activity on the AML and ALL cells and is very effective against B-CLL cells. VNR inhibited the growth of fresh B-CLL cells from 15 of 18 patients, the IC50 doses ranging from 4 ng/ml to 83 microg/ml (doses coinciding with the plasma levels obtained in clinics). These observations strongly suggest that VNR could be useful in clinics for the treatment of B-CLL.
Landini
I
I
Hematology Unit, University Hospital, Florence, Italy.
Bartolozzi
B
B
Banchelli
I
I
Degli Innocenti
A
A
Nocentini
O
O
Bernabei
P A
PA
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology*; D003124:Colorimetry; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D000091344:Filaggrin Proteins; D006801:Humans; D066298:In Vitro Techniques; D007945:Leukemia, Lymphoid / Q000188:drug therapy* / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use* / Q000633:toxicity; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D014747:Vinblastine; D000077235:Vinorelbine