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Toll‐like receptor 7 agonist, Imiquimod, inhibits oral squamous carcinoma cells through apoptosis and necrosis
Author(s) -
Ahn MeeYoung,
Kwon SeongMin,
Cheong Hak Hyun,
Park JongHwan,
Lee Jun,
Min SeungKi,
Ahn SangGun,
Yoon JungHoon
Publication year - 2012
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/j.1600-0714.2012.01158.x
Subject(s) - imiquimod , apoptosis , annexin , cancer research , programmed cell death , flow cytometry , tlr7 , viability assay , microbiology and biotechnology , toll like receptor , biology , immune system , immunology , innate immune system , biochemistry
J Oral Pathol Med (2012) 41 : 540–546 Background: Toll‐like receptor (TLR) agonists have anticancer effect by inducing apoptosis or activating immune cells. In this study, we investigated whether imiquimod, TLR7 agonist, inhibits the proliferation of oral cancer cells. Methods: Toll‐like receptor 7 expression and IL‐6/8 production by imiquimod were examined using RT‐PCR and Enzyme‐linked immunosorbent assay, respectively. Cell viability was examined by MTT assay. To examine apoptotic cell death, Annexin V/PI staining for flow cytometry and Western blot analysis were performed. Necrotic cell death was determined by leakage of lactate dehydrogenase (LDH), HMGB1, and PI staining in imiquimod‐treated oral squamous cell carcinoma (OSCC) cells. Results: Toll‐like receptor7 mRNA was expressed in OSCC cells. Imiquimod induced IL‐6 and IL‐8 production in OSCC cells, suggesting the functional expression of TLR7. Imiquimod inhibited cells proliferation in a dose‐dependent manner. The ratio of annexin V‐positive cells and cleaved caspase‐3/7 was increased by imiquimod treatment in OSCC cells, suggesting that imiquimod‐induced cell death in OSCC cells may be owing to apoptosis. In addition, LDH secretion and PI staining were detected in OSCC cells treated with imiquimod, showing that imiquimod also induced necrotic cell death in the OSCC cells. Conclusions: Imiquimod inhibited effectively the growth of OSCC cells by inducing apoptosis and necrosis.