Effect Of Mda-7/IL-24 On Hematopoietic Malignances

Melanoma differentiation associated gene-7(mda-7) was isolated by Jiang et al from a melanoma cell line induced to differentiate by interferon - β and mezerein. On the basis of its structure, cytokine-like properties, and proposed mode of action, mda-7 has now been classified as IL-24. Since its initial isolation from melanoma cells, the mda-7/IL-24 gene has been studied in numerous other solid tumor types, including carcinoma of the lung, breast, prostate and cervix, consistently demonstrating growth-inhibitory effects on various tumor types. Although mda-7/IL-24 has been a known candidate cancer gene therapeutic molecule, the effects on leukemia remain elusive. We have therefore undertaken a study to better define the significance of mda-7/IL-24 in this disease.We investigated the anti-tumor effects of ectopic expressed mda-7/IL-24 using lipofectamine transfection on human leukemic cells in vitro. Significant decrease of tumor cell viability was observed in Namalwa cells stably transfected with mda-7/IL-24, compared with control cells transfected with pTarget or nontransfected cells. Cell cycle analysis using PI staining indicated an increase in the percentage of the G2/M population and a decrease in the percentage of the S phase population after stably transfection of tumor cells treated with mda-7/IL-24 compared with pTarget-transfected or nontransfected Namalwa cells. Transfection with mda-7/IL-24 also inhibits colony formation in vitro in Namalwa cell lines. Seventy-two hrs after mda-7/IL-24 transfection, a significant increase in Annexin v -positive cells was observed in the Namalwa lines (52.05%±0.62%), compared with pTarget-transfected cells (1.09%±0.34%). However, K562 cells failed to demonstrate any significant change in the number of Annexin v -positive cells. Our results show that mda-7/IL-24 induces growth suppression and apoptosis in Namalwa cells, but not in K562 cells. In stably transfected Namalwa cells, we found growth suppression and apoptosis correlate with an decrease of bcl-2, β-catenin and NF- κB. Taken together, these data...