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Войти в исследования Pharmacological reports : PR · 2024
β-Carboline derivatives are potent against Acute Myeloid Leukemia in vitro and in vivo.
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Bueno Maura Lima Pereira, Foglio Mary Ann, Baréa Paula, de Oliveira Aline Rufino, Sarragiotto Maria Helena, Saad Sara T Olalla, Roversi Fernanda Marconi
Аннотация
BACKGROUND: β-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 β-carboline derivatives containing different substituents at 1- and 3-positions of β-carboline nucleus for their antineoplastic activities in a panel of leukemia cell lines.
METHODS: The cytotoxic effects of the β-carboline derivatives were evaluated in different leukemia cell lines as well as reactive oxygen species (ROS) generation, autophagy, and important signaling pathways.
RESULTS: Treatment with the β-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 β-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.
CONCLUSIONS: Our results indicated that β-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.
METHODS: The cytotoxic effects of the β-carboline derivatives were evaluated in different leukemia cell lines as well as reactive oxygen species (ROS) generation, autophagy, and important signaling pathways.
RESULTS: Treatment with the β-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 β-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.
CONCLUSIONS: Our results indicated that β-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.