Autophagy-mediated anti-tumoral activity of imiquimod in Caco-2 cells

초록

Imiquimod (IMQ) is recognized as a topical immune response modifier compound that enhances immune responses with anti-viral and anti-tumoral activities. Its anti-tumoral effects have been previously demonstrated in a variety of cancer cells, and were identified as indirect responses mediated by the immune modulation Of cutaneous dendritic cells. Recently, the pro-apoptotic activities Of IMQ occuring Via the modulation of bcl-2 family have been reported in several tumor cells. In this Study, we first observed IMQ-initiated autophagy determined by vesicular organelle formation and the generation of LC3-II in Caco-2 human colonic adenocarcinoma cells, which expressing functional TLR7. Additionally, IMQ-induced autophagy resulted in cell death Occurring independently of molecular changes of apoptotic markers. Loxoribine also induced autophagy and autophagy-induced cell death at less potent than IMQ. Moreover. the activation of autophagy by rapamycin induced enhanced cell death in TNF-alphatreated Caco-2 cells, which were autophagy and cell death-resistant. Our results led LIS to Conclude that IMQ exerts a direct effect oil the anti-tumoral activity of Caco-2 cells via autophagy-induced cell death. In conclusion, the modulation of autophagy might be applied in a potential cancer therapy for (be treatment of colon cancer cells. (C) 2009 Elsevier Inc. All rights reserved.

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