β-Carboline derivatives are potent against Acute Myeloid Leukemia in vitro and in vivo

Autor(es)

Bueno, Maura Lima Pereira ; Foglio, Mary Ann ; Barea, Paula ; de Oliveira, Aline Rufino ; Sarragiotto, Maria Helena ; Saad, Sara T. Olalla ; Roversi, Fernanda Marconi

• Tipo de documento: Artigo Científico
• Fonte: PHARMACOLOGICAL REPORTS; v. 76, n. 4, p. 13-pg., 2024-06-20.

Resumo

Background beta-carboline alkaloids exert a distinguished ability to impair cell growth and induce cell death in a variety of cancers and the evaluation of such new therapeutic candidates may denote new possibilities for leukemia treatment. In this present study, we screened 12 beta-carboline derivatives containing different substituents at 1- and 3-positions of beta-carboline nucleus for their antineoplastic activities in a panel of leukemia cell lines.MethodsThe cytotoxic effects of the beta-carboline derivatives were evaluated in different leukemia cell lines as well as reactive oxygen species (ROS) generation, autophagy, and important signaling pathways.ResultsTreatment with the beta-carboline derivatives resulted in a potent antineoplastic activity leading to a reduced cell viability that was associated with increased cell death in a concentration-dependent manner. Interestingly, the treatment of primary mononuclear cells isolated from the peripheral blood of healthy donors with the beta-carboline derivatives showed a minor change in cell survival. The antineoplastic activity occurs by blocking ROS production causing consequent interruption of the PI3K/AKT and MAPK/ERK signaling and modulating autophagy processes. Notably, in vivo, AML burden was diminished in peripheral blood and bone marrow of a xenograft mouse model.ConclusionsOur results indicated that beta-carboline derivatives have an on-target malignant cell-killing activity and may be promising candidates for treating leukemia cells by disrupting crucial events that promote leukemia expansion and chemotherapy resistance. (AU)

• Processo FAPESP: 17/21801-2 - Preditores de gravidade e novos tratamentos para neoplasias da medula óssea
• Beneficiário: Sara Teresinha Olalla Saad
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/25247-5 - Estudo da atividadecitotóxica e antitumoral de fármacos inibidores de MAPK e WNT associados a substâncias naturais em modelos in vitro
• Beneficiário: Maura Lima Pereira Bueno
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 21/05320-0 - Perfil dos universitários brasileiros que fazem uso de cigarro eletrônico: um estudo epidemiológico sobre um consumo proibido
• Beneficiário: Gabriella dos Santos Maximino
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica