Autophagy-mediated anti-tumoral activity of imiquimod in Caco-2 cells.
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 occurring 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-alpha-treated Caco-2 cells, which were autophagy and cell death-resistant. Our results led us to conclude that IMQ exerts a direct effect on 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 the treatment of colon cancer cells.
Yi
Jae Youn
JY
Lab of Modulation of Radiobiological Response, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
Jung
Yu-Jin
YJ
Choi
Sun Shim
SS
Hwang
Jungjin
J
Chung
Eunkyung
E
D000634:Aminoquinolines / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy; D018938:Caco-2 Cells; D006801:Humans; D000077271:Imiquimod; D008024:Ligands; D051199:Toll-Like Receptor 7 / Q000819:agonists*
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D008024:Ligands; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D000077271:Imiquimod