The rare-earth yttrium complex [YR(mtbmp)(thf)] triggers apoptosis via the extrinsic pathway and overcomes multiple drug resistance in leukemic cells

Abstract

A major problem in treating patients with acute lymphoblastic leukemia is the development of drug resistance. In the current study, we investigated the anticancer properties of the novel rare-earth yttrium complex [YR(mtbmp)(thf)] in various established cell lines, and moreover, we identified the involved apoptotic pathway. Further aim was to investigate whether synergistic effects could be reached in combination with the conventional drug vincristine. We used the yttrium complex [YR(mtbmp)(thf)] in cells of leukemia (Nalm-6) and lymphoma (BJAB) and identified the main mechanism of the apoptosis induction by measuring the amount of hypodiploid DNA via FACS Scan analysis. Exposure of BJAB cells to [YR(mtbmp)(thf)] led to a death receptor-mediated reduction of cell viability and induction of apoptosis. The independence of Bcl-2 expression supports the suggestion that the [YR(mtbmp)(thf)]-induced apoptosis is mainly mediated via the extrinsic pathway. The extensive anti-tumor activity of [YR(mtbmp)(thf)] could be underlined by its capability to overcome multiple drug resistance in leukemic cells (Nalm-6) that are characterized by an overexpression of P-glycoprotein. [YR(mtbmp)(thf)] in combination with the conventional drug vincristine displayed impressive synergistic effects. We demonstrate in vitro efficiency of [YR(mtbmp)(thf)] in cells of hematological malignancies and reveal its ability to be a possible agent for polychemotherapy.

Anticancer cytotoxicity assessment of cationic surfactants metal complexes

“…The obtained toxicity values (IC 50 ) showed two characteristics of the tested compounds: 1. The efficiency of the metal complexes depends on the type of the transition metal within the same series [25], i.e., when the cationic surfactant (ligand) is fixed. More the electronegative transition metal is more the anticancer agent effective for growth of huh-7 cells.…”

“…At the different cationic surfactants (different ligand), the alkyl chain length plays an important role in the efficiency of the metal complexes [25][26]. Increasing the alkyl chain length increases the efficiency of the metal complexes as anticancer agents.…”

Cytotoxic lanthanum oxide nanoparticles sensitize glioblastoma cells to radiation therapy and temozolomide: an in vitro rationale for translational studies

“…In terms of the extrinsic pathway, the generation of ROS as a trigger via lanthanum has not been proposed to date as of yet. There are no reports in the literature associating lanthanum-based NPs to the extrinsic pathway, although other REE free ions such, as gadolinium 30 and yttrium 31 in other tumor types, have been linked with the extrinsic apoptosis through ROS generation. In addition to apoptosis, which occurs outside the nucleus, our results suggest that these NPs may also cause direct nuclear damage based on our electron microscopy and western blotting results.…”

Anti-proliferative and Apoptotic Effects of morin in human Leukemia cell lines (HUT-78)

“…HuT-78 cells were derived from peripheral blood of a 50-years old Caucasian male patient with sezary syndrome. The cells exhibit features of mature T-cell line with inducer/helper phenotype and release T-cell growth factor (IL-2) [24]. Nalm-6 cell established from the peripheral blood of a 19-year-old man with http://www.ispacs.com/journals/ijcmb/2013/ijcmb-00001/ International Scientific Publications and Consulting Services acute lymphoblastic leukemia (ALL) in relape in 1976 [25].…”