Enhanced uptake of antisense oligonucleotides using cationic liposomes and the apoptotic effect of idarubicin in K-562 cell line

VELLÓN L, GONZÁLEZ CID M, KARARA A, NEBEL MDE C, CUELLO MT, LARRIPA I.

LEUKEMIA RESEARCH

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2002 vol. 26 p. 669 - 676

0145-2126

We have evaluated the apoptotic and DNA damaging activity of Idarubicin (IDA) on K-562 cells alone and following the uptake of modified antisense-oligodeoxynucleotides (AS-ODNs) targeting b3a2 mRNA of bcr/abl hybrid gene, after treatment with AS-ODNs/DCChol-DOPE (liposomes) complexes. The uptake of FITC-labeled oligonucleotide-liposomes complexes (FITC-ODNs/DCChol-DOPE) was analyzed by flow cytometry and fluorescence microscopy. Both techniques indicated cytoplasmic accumulation of labeled liposome complexes following 24h of exposure. In absence of liposomes, AS-ODNs uptake was minimal. Pre-treatment of cells with AS-ODNs/DCChol-DOPE increased the capability of IDA to induce apoptosis as determined by morphology and the comet assay. In contrast, the use of a non-sense oligodeoxynucleotide conjugated with liposomes, in the presence of IDA, did not increase K-562 cell apoptosis. Nevertheless, DNA damage in IDA treated cells was not related to ODNs/liposomes pre-treatment, as determined by the comet assay. Our data suggests that DCChol-DOPE increases the uptake of ODNs in K-562 cells, and these modified AS-ODNs increase IDA induced apoptosis by decreasing p210(bcr/abl) levels in K-562 cells.