title: Rituximab increases the cytotoxicities of vincristine and hydroxyurea through caspase-dependent and caspase-independent cell death, respectively.
abstract: In the treatment of B cell non-Hodgkin's lymphoma, rituximab is used in combination with different chemotherapeutics to improve its efficacy, but the mechanisms involved are not fully understood. The authors examined the mechanism by which rituximab combined with hydroxyurea or vincristine induces cell death in the human Burkitt's lymphoma Ramos cell line. Cell death was analyzed by phosphatidylserine exposure, caspase activation, and mitochondrial membrane changes. Their results indicate that the cell death initiated by the combination of rituximab and hydroxyurea is caspase-independent. In contrast, preincubation of the cells with the same concentrations of caspase inhibitors used with hydroxyurea eliminated the synergistic effect of the rituximab and vincristine combination. This was confirmed by the presence of the active fragment of caspase-3 in vincristine-treated cells. These preliminary results demonstrate that rituximab can activate different downstream signals to induce direct cell effects. Furthermore, the findings support the important role of mitochondria in the regulation of both pathways.
authors.affiliation: Cell Biology Research Group, Biotechnology Research Center , Twisha, Tripoli, Libya .
authors.forename: Salah
authors.initials: S
authors.lastname: Tabal
authors.forename: Abdulrhman
authors.initials: A
authors.lastname: Elbanani
authors.forename: Mohamed
authors.initials: M
authors.lastname: Deyab
authors.forename: Abdulmunem
authors.initials: A
authors.lastname: Abulayha
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000473:pathology*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D000069283:Rituximab / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D061945:Caspase Inhibitors; D000069283:Rituximab; D014750:Vincristine; D020169:Caspases; D006918:Hydroxyurea
keywords: Rituximab; caspases; hydroxyurea; mitochondria; vincristine