Immune Netw.  2011 Dec;11(6):383-389. 10.4110/in.2011.11.6.383.

Cellular Mechanism of Newly Synthesized Indoledione Derivative-induced Immunological Death of Tumor Cell

Affiliations
  • 1Office of Biomedical Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea. andyjosh@skku.edu
  • 2College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea.

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.

Keyword

Indoledione derivatives; Carleticulin; Immunological death of tumor cell; Dendritic cell

MeSH Terms

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
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4
Tumor Necrosis Factor-alpha
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