Modulation of reactive oxygen species by antioxidants in chronic myeloid leukemia cells enhances imatinib sensitivity through survivin downregulation.
Survivin, a member of the inhibitor of apoptosis protein family and a target for new drugs, is modulated by reactive oxygen species in several types of neoplasms including leukemias. The aim of this study is to find mechanisms to enhance sensitivity to imatinib in imatinib-responsive cells. In this study, we demonstrated through fluorescein isothiocyanate-labeled annexin V for apoptotic cells detection and western blotting that by inhibiting catalase activity, imatinib apoptosis induction was significantly enhanced (P<0.05) through diminishing survivin expression in K562 cells. These findings might be of clinical relevance and might help improve the chemotherapeutic use of imatinib mesylate.
Kwee
Jolie Kiemlian
JK
Laboratório de Hematologia Celular e Molecular, Serviço de Hematologia, Hospital do Câncer, Instituto Nacional de Câncer, Rio de Janeiro-RJ, Brazil. jkwee@inca.gov.br
Luque
Diogo Gomes
DG
Ferreira
Ana Carolina dos Santos
AC
Vasconcelos
Flavia da Cunha
FC
Silva
Karina Lani
KL
Klumb
Claudete Esteves
CE
Maia
Raquel Ciuvalschi
RC
D000640:Amitrole / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001549:Benzamides; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D000068877:Imatinib Mesylate; D051034:Inhibitor of Apoptosis Proteins; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077022:Survivin
D000970:Antineoplastic Agents; D000975:Antioxidants; C107489:BIRC5 protein, human; D001549:Benzamides; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010879:Piperazines; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D000077022:Survivin; D019328:Buthionine Sulfoximine; D000068877:Imatinib Mesylate; D000640:Amitrole