HA14-1, a small molecule Bcl-2 antagonist, induces apoptosis and modulates action of selected anticancer drugs in follicular lymphoma B cells.

Abstract

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.