title: Flavopiridol-induced iNOS downregulation during apoptosis of chronic lymphocytic leukemia cells is caspase-dependent.
abstract: We previously reported that flavopiridol-induced apoptosis of B cell chronic lymphocytic leukemia (CLL) patients' cells ex vivo is associated with downregulation of both the inducible nitric oxide (NO) synthase (iNOS) that produces the antiapoptotic molecule NO, and the CDK inhibitor p27kip1 that is thought to block the cell cycle of CLL cells. Here, we show that iNOS downregulation is caspase-dependent and thus can be considered as one of the effector mechanisms of apoptosis, but not a primary triggering event induced by flavopiridol. Furthermore, we also find that this flavone favors the entry into the S and G2 phases of the cell cycle of a subpopulation of the leukemic cells, confirming that flavopiridol might be useful for improving the efficacy of cell cycle-dependent cytostatic agents in the therapy of CLL.
authors.affiliation: INSERM U872 (équipe 18), Université Pierre et Marie Curie-Paris 6, Paris, France. cbillard@bhdc.jussieu.fr
authors.forename: Christian
authors.initials: C
authors.lastname: Billard
authors.forename: Faouzia
authors.initials: F
authors.lastname: Menasria
authors.forename: Claire
authors.initials: C
authors.lastname: Quiney
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Faussat
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kolb
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics; D010880:Piperidines / Q000494:pharmacology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C077990:alvocidib; D052247:Nitric Oxide Synthase Type II; D020169:Caspases