The anti-tumor ether lipid edelfosine is the prototype of a novel generation of promising
anticancer drugs that has been shown to be an effective anti-tumor agent in numerous
malignancies. However, several cancer types display resistance to different anti-tumor
compounds due to multi-drug resistance (MDR), which is a major drawback in anticancer
therapy.
The leukemic cell line K-562 shows resistance to edelfosine, which can be overcome by the
use of nanotechnology. The present paper describes the rate and mechanism of
internalization of free and nano-encapsulated edelfosine. The molecular mechanisms
underlying this cell death is described in the present paper by characterization of several
molecules implied in the apoptotic and autophagic pathways (PARP, LC3IIB, Caspases-3, -
9 and -7) and the pattern of expression is compared with cell induction in a sensitive cell
line HL-60.
The results showed different internalization patterns in both cells. Clathrin and lipid raftmediated
endocytosis were observable in edelfosine uptake whereas these mechanism were
not visible in the uptake of lipid nanoparticles which might suffer phagocytosis and
macropinocytosis. Both treatments endorsed caspase-mediated apoptosis in HL-60 cells but
this cell death was not observed in K-562 cells. Moreover, an important increase in
autophagic vesicles was visible in K-562 cells. Thus, this mechanism might be implicated
in the overcoming of K-562 resistance to the treatment by lipid nanoparticles
