These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Cationic lipids reduce time and dose of c-myc antisense oligodeoxynucleotides required to specifically inhibit Burkitt's lymphoma cell growth.
    Author: Williams SA, Chang L, Buzby JS, Suen Y, Cairo MS.
    Journal: Leukemia; 1996 Dec; 10(12):1980-9. PubMed ID: 8946941.
    Abstract:
    Burkitt's lymphoma is characterized by a translocation of the c-myc gene with one of the immunoglobulin loci which activates overexpression of the c-myc oncogene. Antisense-oligodeoxynucleotides (AS-ODNs) offer the potential to block specific c-myc gene expression within lymphoma cells, but often exhibit a low efficiency of AS-ODN uptake. In this study, a polycationic lipid reagent, Lipofectamine (LFM), was utilized as a vehicle to increase efficiency of delivery, decrease the time needed to observe an inhibitory effect, and decrease the AS-ODN dose. The objective was to develop a more efficient and rapid in vitro AS-ODN strategy to inhibit proliferation of c-myc-dependent lymphoma cells and to test the specificity of Burkitt's lymphoma cell line-directed AS-ODNs for potential use as molecular purging agents in bone marrow transplantation. Proliferation assays were performed to determine the inhibitory effect of the AS-ODNs on two Burkitt's lymphoma cell lines with different chromosomal translocations, Daudi and ST486, in medium containing 8.5 microM LFM. AS-ODNs at a concentration of 0.36 microM induced a significant decrease in proliferation for both cell lines using the specific AS-ODN for each respective translocation. Within 5 h, Daudi responded to its specific AS-ODN/lipid complexes with a 35% decrease in proliferation, compared to cells which received no treatment or Daudi-specific AS-ODN without LFM (P = 0.0001). Daudi showed an insignificant decrease in proliferation when treated with an AS-ODN specific for the ST486 translocation (4%, P = 0.26). ST486 proliferation was decreased by 52% when treated with the specific antisense for ST486 compared to no treatment or ST486-specific AS-ODN without LFM (P < 0.003). Treatment with the AS-ODN specific for Daudi showed an insignificant 4% decrease (P = 0.42). Controls, including sense ODN for structure, reverse AS-ODN for structure and base composition, and AS-ODN without LFM, did not produce a significant change in cells treated with LFM alone or cells receiving no treatment. Clonogenic assays of both Daudi and ST486 treated with their specific AS-ODNs revealed a 50% inhibition of colony formation after the 5 h incubation as compared to no treatment. Confocal laser scanning microscopy verified that cellular uptake of AS-ODN was enhanced by cationic lipids. Immunoblot analysis showed a 63 +/- 5% and a 50 +/- 3% reduction in intracellular c-myc levels for Daudi and ST486, respectively, when their respective AS-ODNs were administered. Normal bone marrow progenitors were unaffected by the ODN/LFM complexes. These results suggest that the specific c-myc AS-ODN/LFM complexes inhibit c-myc-dependent tumor proliferation at an earlier time and at a lower dose compared to no lipid facilitation. This approach may form the basis for utilizing specific AS-ODN/LFM therapy either alone or in a cocktail of other agents as an ex vivo molecular purging approach to autologous stem cell transplantation in Burkitt's lymphoma.
    [Abstract] [Full Text] [Related] [New Search]