ArticleMolecular pharmacology2010
Melanoma differentiation associated gene-7/interleukin-24 potently induces apoptosis in human myeloid leukemia cells through a process regulated by endoplasmic reticulum stress.
Article in Molecular pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- T helper 2 cell-directed immunotherapy eliminates precancerous skin lesions.The Journal of clinical investigation · 2025Article
- Review
- PIKFYVE inhibitors trigger interleukin-24-dependent cell death of autophagy-dependent melanoma.Molecular oncology · 2024Article
- Suppression of antitumor cytokine IL‑24 by PRG4 and PAI‑1 may promote myxoid liposarcoma cell survival.Biomedical reports · 2023Article
- Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases.International journal of molecular sciences · 2022Review
- Engineering T Cells to Express Tumoricidal MDA-7/IL24 Enhances Cancer Immunotherapy.Cancer research · 2021Article
- ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both?Biomolecules · 2021Review
- Recent insights into apoptosis and toxic autophagy: The roles of MDA-7/IL-24, a multidimensional anti-cancer therapeutic.Seminars in cancer biology · 2020Review
- Mechanism of internalization of MDA-7/IL-24 protein and its cognate receptors following ligand-receptor docking.Oncotarget · 2019Article
- Cotargeting BCL-2 and PI3K Induces BAX-Dependent Mitochondrial Apoptosis in AML Cells.Cancer research · 2018Article
- Role of MDA-7/IL-24 a Multifunction Protein in Human Diseases.Advances in cancer research · 2018Review
- Article
- Induction of endoplasmic reticulum stress as a strategy for melanoma therapy: is there a future?Melanoma management · 2014Review
- Molecular targets and signaling pathways regulated by interleukin (IL)-24 in mediating its antitumor activities.Journal of molecular signaling · 2013Article
- Targeting breast cancer-initiating/stem cells with melanoma differentiation-associated gene-7/interleukin-24.International journal of cancer · 2013Article
- Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism.Cancer research · 2013Article
- Dihydroarteminsin-induced apoptosis is not dependent on the translocation of Bim to the endoplasmic reticulum in human lung adenocarcinoma cells.Pathology oncology research : POR · 2012Article
- Article
- Neural transmembrane protease and endothelial Gs protein activation in cell contact-dependent signaling between neural stem/progenitor cells and brain endothelial cells.The Journal of biological chemistry · 2012Article
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 (IL-24), a member of the IL-10 cytokine gene family, preferentially induces cell death in neoplastic epithelial cells types while sparing their normal counterparts. The effects of mda-7/IL-24 in acute myeloid leukemia (AML) cells have not been extensively characterized. Treatment with recombinant GST-MDA-7/IL-24 potently induced apoptosis in diverse myeloid leukemia cell types including U937, HL60, MV4-11, EOL-1, and MLL/ENL cells. MDA-7/IL-24 also markedly induced apoptosis in and suppressed the colony-forming capacity of primary AML blasts but exerted minimal toxicity toward normal CD34(+) hematopoietic progenitor cells. MDA-7/IL-24 lethality was associated with pronounced endoplasmic reticulum (ER) stress induction in leukemia cell lines and primary AML blasts, manifested by the accumulation of growth arrest and DNA damage-inducible protein 34 (GADD34), 78-kDa glucose-regulated protein (GRP78)/BiP, inositol-requiring enzyme 1α (IRE1α), and eukaryotic initiation factor 2α phosphorylation. It is noteworthy that short hairpin RNA (shRNA) knockdown of IRE1α, GADD34, or GRP78/BiP significantly enhanced MDA-7/IL-24-mediated apoptosis, indicating a protective role for these molecules against MDA-7/IL-24 lethality. MDA-7/IL-24 also down-regulated the antiapoptotic protein Mcl-1 and sharply increased expression of the proapoptotic proteins Bim and Noxa. Ectopic Mcl-1 expression or shRNA knockdown of Bim or Noxa significantly attenuated MDA-7/IL-24-mediated leukemia cell death. Finally, knockdown of Bax or Bak significantly reduced MDA-7/IL-24 lethality. Together, these findings indicate that MDA-7/IL-24 potently induces apoptosis in human myeloid leukemia cells through a process regulated by ER stress induction, Mcl-1 down-regulation, and Bim and Noxa up-regulation. They also suggest that MDA-7/IL-24 warrants further investigation in myeloid leukemia.
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