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KMID : 0923620110110060383
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Immune Network
2011 Volume.11 No. 6 p.383 ~ p.389
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Cellular Mechanism of Newly Synthesized Indoledione Derivative-induced Immunological Death of Tumor Cell
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Oh Su-Jin
Ryu Chung-Kyu
Baek So-Young
Lee Hyun-Ah
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Abstract
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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?M) with carleticulin induction. And EY-6 induced the secretion of IFN-? but not of TNF-? 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.
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KEYWORD
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Indoledione derivatives, Carleticulin, Immunological death of tumor cell, Dendritic cell
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