Multitarget Effects of Quercetin in Leukemia

Autor(es)

Maso, Victor ^[1] ; Calgarotto, Andrana Karla ^[1] ; Franchi, Jr., Gilberto Carlos ^[2] ; Nowill, Alexandre Eduardo ^[2] ; Latuf Filho, Paulo ^[3] ; Vassallo, Jose ^[3] ; Olalla Saad, Sara Teresinha ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Hemoctr, Hematol & Hemotherapy Ctr, Sao Paulo - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Oncohematol Child Res Ctr, Sao Paulo - Brazil

^[3] FCM Unicamp, CIPED, Fac Med Sci, Dept Pathol, Lab Invest & Mol Pathol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Cancer Prevention Research; v. 7, n. 12, p. 1240-1250, DEC 2014.
• Citações Web of Science: 20

Resumo

This study proposes to investigate quercetin antitumor efficacy in vitro and in vivo, using the P39 cell line as a model. The experimental design comprised leukemic cells or xenografts of P39 cells, treated in vitro or in vivo, respectively, with quercetin; apoptosis, cell-cycle and autophagy activation were then evaluated. Quercetin caused pronounced apoptosis in P39 leukemia cells, followed by Bcl-2, Bcl-xL, Mcl-1 downregulation, Bax upregulation, and mitochondrial translocation, triggering cytochrome c release and caspases activation. Quercetin also induced the expression of FasL protein. Furthermore, our results demonstrated an antioxidant activity of quercetin. Quercetin treatment resulted in an increased cell arrest in G(1) phase of the cell cycle, with pronounced decrease in CDK2, CDK6, cyclin D, cyclin E, and cyclin A proteins, decreased Rb phosphorylation and increased p21 and p27 expression. Quercetin induced autophagosome formation in the P39 cell line. Autophagy inhibition induced by quercetin with chloroquine triggered apoptosis but did not alter quercetin modulation in the G(1) phase. P39 cell treatment with a combination of quercetin and selective inhibitors of ERK1/2 and/or JNK (PD184352 or SP600125, respectively), significantly decreased cells in G(1) phase, this treatment, however, did not change the apoptotic cell number. Furthermore, in vivo administration of quercetin significantly reduced tumor volume in P39 xenografts and confirmed in vitro results regarding apoptosis, autophagy, and cell-cycle arrest. The antitumor activity of quercetin both in vitro and in vivo revealed in this study, point to quercetin as an attractive antitumor agent for hematologic malignancies. (C)2014 AACR. (AU)

• Processo FAPESP: 08/58615-2 - Investigação dos efeitos biológicos e farmacológicos da quercetina em células de pacientes com Mielodisplasia e Leucemia Mielóide Aguda
• Beneficiário: Victor Maso
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto