HA14-1, a small molecule Bcl-2 antagonist, induces apoptosis and modulates action of selected anticancer drugs in follicular lymphoma B cells.
The BCL-2 overexpression is a hallmark of follicular lymphoma (FL). Since patients with FL often suffer from resistant to chemotherapy refractory disease, the development of new regimens is required. Herein, we analyze for the first time the effects of a B-cell lymphoma 2 (Bcl-2) antagonist, HA14-1, alone and in combination with antineoplastic agents commonly used against follicular lymphoma, in human FL cell lines with t(14;18). All cell lines tested were sensitive to HA14-1-induced cytotoxicity and apoptosis, as depicted by morphological changes, SYTO16/PI staining, oligonucleosomal DNA fragmentation and loss of Deltapsi(m). Moreover, HA14-1 significantly enhanced dexamethasone- and doxorubicin-mediated (in schedule independent and dependent manner, respectively), but not vincristine-mediated cytotoxicity and apoptosis.
Skommer
Joanna
J
Department of Clinical Microbiology, University of Kuopio, Harjulantie 1 C, FIN-70211 Kuopio, Finland. joannaskommer@yahoo.com
Wlodkowic
Donald
D
Mättö
Mikko
M
Eray
Mine
M
Pelkonen
Jukka
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000378:metabolism*; D008224:Lymphoma, Follicular / Q000178:diet therapy / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001578:Benzopyrans; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin