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Immune Netw. 2011 Dec;11(6):383-9. doi: 10.4110/in.2011.11.6.383. Epub 2011 Dec 31.

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

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1
Office of Biomedical Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, 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 µM) with carleticulin induction. And EY-6 induced the secretion of IFN-γ but not of TNF-α 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.

KEYWORDS:

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

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