Induction of apoptosis in the human mast cell leukemia cell line HMC-1 by various antineoplastic drugs.
Mast cell leukemia (MCL) is a rare disorder characterized by rapid disease progression, resistance against conventional cytoreductive drugs, and short survival. In an attempt to identify drugs that show significant antiproliferative effects on neoplastic mast cells (MC), we exposed the MCL-derived cell line HMC-1 to various cytotoxic drugs including 2-chlorodeoxyadenosine [2CdA], fludarabine and cytosine arabinoside [ARA-C]. The effects of these drugs on 3H-thymidine incorporation, electron microscopic signs of apoptosis, and DNA fragmentation in HMC-1 cells, were analyzed. As assessed by 3H-thymidine incorporation, all drugs produced inhibition of proliferation in HMC-1 cells with the following rank order of potency: ARA-C > doxorubicine > 2-CdA > etoposide > vincristine > fludarabine > cisplatin. Fludarabin, cisplatin, etoposide and 2-CdA also induced ladder-type fragmentation of DNA, endonuclease activity in a Tunel assay, and electron microscopic signs of apoptosis in HMC-1 cells. Together, our data show that various cytostatic drugs can induce apoptosis and inhibition of proliferation in the human MCL cell line HMC-1. Whether these drugs, alone or in combination, are also effective in patients with MCL, remains to be determined.
Samorapoompichit
Puchit
P
Institute of Histology and Embryology, The University of Vienna, Vienna, Austria.
Steiner
Marianne
M
Lucas
Trevor
T
Wachtler
Franz
F
Schedled
Andreas
A
Sperr
Wolfgang R
WR
Valent
Peter
P
D015762:2-Chloroadenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage; D003561:Cytarabine / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007946:Leukemia, Mast-Cell / Q000473:pathology*; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014750:Vincristine / Q000008:administration & dosage
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D009363:Neoplasm Proteins; D003561:Cytarabine; D015762:2-Chloroadenosine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D004706:Endodeoxyribonucleases; D014740:Vidarabine; C055994:2-chloro-3'-deoxyadenosine; C024352:fludarabine; D002945:Cisplatin