title: Biological effects of Atra and Arsenic Trioxide on short term cultures of non-M3 leukemic blasts.
abstract: The efficacy of All-Trans Retinoic Acid (Atra) and Arsenic Trioxide (As(2)O(3)) in the treatment of Acute Promyelocytic Leukemia (APL) is well known. Further, these drugs inhibit cell growth and induce apoptosis in several cell lines, but few data are reported on leukemic blasts. The aim of this study was to evaluate the biological effects on non-M3 Acute Myeloid Leukemia (AML) cells. Blasts of six patients, after exposition to Atra and As(2)O(3) were tested for growth inhibition, induction of apoptosis and change in cell cycle distribution, evaluating cell viability, percentage of apoptotic cells and of blasts positive for Ki-67 and BrdU. In the present study we demonstrated that either Atra or As(2)O(3) inhibit leukemic cells proliferation by induction of apoptosis. The effects are time and dose dependent. We did not observe additive or synergistic effects with the combination of the drugs. Further, our results showed that Atra and As(2)O(3) have effects on cell cycle distribution reducing S-phase and proliferating cells. These results should be taken in to account preparing future laboratory and clinical experimental protocols that associate these drugs with antineoplastic agents with different cell cycle specificity.
authors.affiliation: Program of Innovative Therapy in Oncology and Hematology, Department of Oncology and Hematology, University of Modena, Policlinico, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Cosenza
authors.forename: Monica
authors.initials: M
authors.lastname: Civallero
authors.forename: Stefano
authors.initials: S
authors.lastname: Sacchi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Marcheselli
authors.forename: Samantha
authors.initials: S
authors.lastname: Pozzi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D016196:S Phase; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D001152:Arsenicals; D019394:Ki-67 Antigen; D010087:Oxides; D014212:Tretinoin; D001973:Bromodeoxyuridine; D000077237:Arsenic Trioxide