title: Cytosine arabinoside potentiates the apoptotic effect of bendamustine on several B- and T-cell leukemia/lymphoma cells and cell lines.
abstract: Bendamustine and cytosine arabinoside (ara-c) are commonly used cytotoxic agents with unique mechanisms of action. We have previously reported a striking additive cytotoxic effect of the consecutive combination of bendamustine and ara-c in mantle cell lymphoma (MCL) cell lines. In the present study, cell lines of follicular lymphoma (DOHH-2), chronic lymphocytic leukemia/lymphoma (EHEB), diffuse large B-cell lymphoma (SU-DHL-4), T-cell leukemia/lymphoma (JURKAT and KARPAS-299) and MCL (JEKO-1 and GRANTA-519) were exposed to the two single drugs or the drugs combined, given simultaneously and consecutively. Peripheral blood chronic lymphocytic leukemia (CLL) B-cells from five patients were also analyzed. Apoptosis, cell proliferation/metabolic activity and mitochondrial damage were evaluated. The combination index (CI) was used to assess synergy between the drugs. Bendamustine exhibited a relevant cytotoxic effect that was dose- and time-dependent, except for SU-DHL-4 and T-cell lymphoma cells. The addition of ara-c after bendamustine significantly potentiated the single-drug cytotoxic effect of bendamustine on all cell lines, including 17p - CLL B-cells, JURKAT and SU-DHL-4, the latter presenting the highest synergism (CI < 0.01). Bendamustine and ara-c are highly synergistic on T- and B-cell lymphoma cells and cell lines, similar to MCL, overcoming resistance to the single agents.
authors.affiliation: Department of Cellular Therapies and Hematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Castegnaro
authors.forename: Carlo
authors.initials: C
authors.lastname: Visco
authors.forename: Katia
authors.initials: K
authors.lastname: Chieregato
authors.forename: Martina
authors.initials: M
authors.lastname: Bernardi
authors.forename: Elena
authors.initials: E
authors.lastname: Albiero
authors.forename: Cristina
authors.initials: C
authors.lastname: Zanon
authors.forename: Domenico
authors.initials: D
authors.lastname: Madeo
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000069461:Bendamustine Hydrochloride; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D015448:Leukemia, B-Cell / Q000188:drug therapy; D015458:Leukemia, T-Cell / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D016399:Lymphoma, T-Cell / Q000188:drug therapy; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D009588:Nitrogen Mustard Compounds; D003561:Cytarabine; D000069461:Bendamustine Hydrochloride