RESUMO
There is a variety of antineoplastic drugs that are based on natural compounds from ecological niches with high evolutionary pressure. We used two cell lines (Jurkat J16 and Ramos) in a screening to assess 300 different naturally occurring compounds with regard to their antineoplastic activity. The results of the compounds 4,6-dibromo-2-(2',4'-dibromophenoxy)phenol (P01F03), 4,5,6-tribromo-2-(2',4'-dibromophenoxy)phenol (P01F08), and 5-epi-nakijinone Q (P03F03) prompted us to perform further research. Using viability and apoptosis assays on the cell lines of primary human leukemic and normal hematopoietic cells, we found that P01F08 induced apoptosis in the cell lines at IC50 values between 1.61 and 2.95 µM after 72 h. IC50 values of peripheral blood mononuclear cells (PBMNCs) from healthy donors were higher, demonstrating that the cytotoxicity in the cell lines reached 50%, while normal PBMNCs were hardly affected. The colony-forming unit assay showed that the hematopoietic progenitor cells were not significantly affected in their growth by P01F08 at a concentration of 3 µM. P01F08 showed a 3.2-fold lower IC50 value in primary leukemic cells [acute myeloid leukemia (AML)] compared to the PBMNC of healthy donors. We could confirm the antineoplastic effect of 5-epi-nakijinone Q (P03F03) on the cell lines via the induction of apoptosis but noted a similarly strong cytotoxic effect on normal PBMNCs.
Assuntos
Antineoplásicos/uso terapêutico , Fenol/uso terapêutico , Adulto , Idoso , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Células HL-60 , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Células Jurkat , Leucemia Mieloide Aguda/tratamento farmacológico , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Células THP-1RESUMO
Carbon nanodots (CNDs) comprise a class of next generation nanomaterials with a wide variety of potential applications. Here, we report on their uptake into primary hematopoietic cells from three normal donors and malignant cells from five patients with de novo acute myeloid leukemia (AML). A significant CND uptake was observed in all cell types of the normal and leukemic cells. Still, the uptake was significantly smaller for the CD34+ and CD33+ myeloid subsets of the malignant cell population as compared to the normal blood-derived CD34+ and CD33+ cells. For the T and B lymphoid cell populations as defined by CD3 and CD19 within the leukemic and normal samples a similar uptake was observed. The CNDs accumulate preferentially in small clusters in the periphery of the nucleus as already shown in previous studies for CD34+ progenitor/stem cells and human breast cancer cells. This particular subcellular localization could be useful for targeting the lysosomal compartment, which plays a pivotal role in the context of autophagy associated survival of AML cells. Our results demonstrate the usability of CNDs beyond their application for in vitro and in vivo fluorescence labeling or drug delivery into normal and malignant cells.