[Induction of apoptosis in human head and neck cancer cell lines by an active component of OK-432 through p53-independent pathway via toll-like receptor (TLR) 4 signaling].
OK-PSA, an active component of OK-432, induces anti-tumor immunity via Toll-like receptor (TLR) 4/MD-2 complex. In the current study, we evaluated the effect of the OK-PSA on human head and neck cancer cell lines. Twelve cancer cell lines including 7 squamous cell carcinoma (SCC) cell lines and 5 salivary gland cancer (SGC) cell lines were examined. The quantitative real-time PCR analysis revealed that TLR4 mRNA was expressed in all 12 cell lines, and that MD-2 mRNA was expressed in 5 cell lines. OK-PSA stimulation resulted in the activation of NF-kappaB in the 4 SCC cell lines which express both TLR4 and MD-2 genes, and in 5 SGC cell lines which express at least TLR4 gene independently of MD-2 expression. In these OK-PSA-responsive cell lines, OK-PSA activated caspase-1, caspase-3 and caspase-8, and induced apoptosis. OK-PSA-induced apoptosis were observed even in a SGC cell line in which p53 is mutated and its function is impaired. These findings strongly suggest that OK-PSA induces apoptosis by the activation of caspases through p53-independent pathway via TLR4 signaling in head and neck cancer cells.
Tano
Tomoyuki
T
Dept. of Therapeutic Regulation for Oral Tumors, Institute of Health Bioscience, University of Tokushima.
Okamoto
Masato
M
Oshikawa
Tetsuya
T
Ahmed
Sharif Uddin
SU
Sasai
Akiko
A
Sato
Mitsunobu
M
D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D045744:Cell Line, Tumor; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000502:physiology; D016328:NF-kappa B / Q000032:analysis; D010844:Picibanil / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology*
D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D010844:Picibanil