Cellular Mechanism of Newly Synthesized Indoledione Derivative-induced Immunological Death of Tumor Cell.
- Author:
Su Jin OH
1
;
Chung Kyu RYU
;
So Young BAEK
;
Hyunah LEE
Author Information
- Publication Type:Original Article
- Keywords: Indoledione derivatives; Carleticulin; Immunological death of tumor cell; Dendritic cell
- MeSH: Animals; Bone Marrow; Cell Death; Colonic Neoplasms; Cross-Priming; Dendritic Cells; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cells; Homicide; Interleukin-4; Mice; Phenotype; Tumor Necrosis Factor-alpha
- From:Immune Network 2011;11(6):383-389
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND: EY-6 is one of the newly synthesized indoledione derivatives to induce tumor cell-specific cell death. In this study, we investigated the mechanism of immunological death induced by EY-6 at mouse colon cancer cell as well as at the normal immune cell represented by dendritic cell. METHODS: C57BL/6 mouse syngeneic colon cancer cell MC38 was treated with EY-6, and analyzed by MTT for viability test, flow cytometry for confirming surface expressing molecules and ELISA for detection of cytokine secretion. Normal myeloid-dendritic cell (DC) was ex vivo cultured from bone marrow hematopoietic stem cells of C57BL/6 mice with GM-CSF and IL-4 to analyze the DC uptake of dead tumor cells and to observe the effect of EY-6 on the normal DC. RESULTS: EY-6 killed the MC38 tumor cells in a dose dependent manner (25, 50 and 100 microM) with carleticulin induction. And EY-6 induced the secretion of IFN-gamma but not of TNF-alpha from the MC38 tumor cells. EY-6 did not kill the ex-vivo cultured DCs at the dose killing tumor cells and did slightly but not significantly induced the DC maturation. The OVA-specific cross-presentation ability of DC was not induced by chemical treatment (both MHC II and MHC I-restricted antigen presentation). CONCLUSION: Data indicate that the EY-6 induced tumor cell specific and immunological cell death by modulation of tumor cell phenotype and cytokine secretion favoring induction of specific immunity eliminating tumor cells.
