Abstract
Ruthenium atoms located in the surfaces of carbosilane dendrimers markedly increase their anti-tumor properties. Carbosilane dendrimers have been widely studied as carriers of drugs and genes owing to such characteristic features as monodispersity, stability, and multivalence. The presence of ruthenium in the dendrimer structure enhances their successful use in anti-cancer therapy. In this paper, the activity of dendrimers of generation 1 and 2 against 1301 cells was evaluated using Transmission Electron Microscopy, comet assay and Real Time PCR techniques. Additionally, the level of reactive oxygen species (ROS) and changes of mitochondrial potential values were assessed. The results of the present study show that ruthenium dendrimers significantly decrease the viability of leukemia cells (1301) but show low toxicity to non-cancer cells (peripheral blood mononuclear cells—PBMCs). The in vitro test results indicate that the dendrimers injure the 1301 leukemia cells via the apoptosis pathway.
Highlights
Among all blood cancers—acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL) [1,2]—treatment of ALL is the most effective
The number of living 1301 cells decreased significantly when 5 μmol/L CRD13 or 10 μmol/L CRD27 was present in the cell suspension (Figure 1)
Ruthenium can react with DNA and damage it [34]. This effect has been observed with different ruthenium compounds [24,25]; we examined the ability of metallodendrimers CDR13 and CDR27 to damage DNA in 1301 cells by comet assays
Summary
Among all blood cancers—acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL) [1,2]—treatment of ALL is the most effective. The survival rate of patients with this type of cancer has increased significantly, especially among children. Despite wide knowledge and use of steroid and chemotherapeutic treatments of cancers, many ALL patients are not yet cured [3,4]. This remains the main cause of mortality, notably among children [5]. Leukemia belongs to the group of cancers that develop secondary resistance to chemotherapy. Overexpression of Mcl-1, Bcl-xL, and Bcl-2, members of the anti-apoptotic protein family, is responsible for cancer cell resistance to chemotherapy [7,8,9]
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