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

作者：Yi Jae Youn; Jung Yu Jin; Choi Sun Shim; Hwang Jungjin; Chung Eunkyung^*

来源：Biochemical and Biophysical Research Communications, 2009, 386(3): 455-458.

DOI：10.1016/j.bbrc.2009.06.046

• Imiquimod
• TLR7
• Autophagy
• Anti-tumoral activity
• TNF-alpha
• Apoptosis
• 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 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.

• 出版日期2009-8-28