Abstract A134: Honokiol targets STAT3 in head and neck squamous cell carcinoma Free

A134

Head and neck squamous cell carcinoma (HNSCC) is a commonly occurring malignancy associated with severe morbidity, persistently high mortality rates, frequent recurrence, and the appearance of second primary tumors. Honokiol, a naturally occurring compound that is derived from the plant, Magnolia officinalis, which has been used in traditional Chinese medicine, has been shown to have anticancer activity in various models and to inhibit nuclear factor kappa B (NFκB), an oncogenic transcription factor. Crosstalk between NFκB and another transcription factor, signal transducer and activator of transcription (STAT)-3, has been demonstrated in HNSCC. Furthermore, NFκB and STAT3 have been found to directly interact in certain cell lines and to have various target genes, including proteins that regulate apoptosis, the cell cycle, and tumor angiogenesis, in common. Therefore, we hypothesized that honokiol might be useful in targeting STAT3, a protein that is known to promote growth, invasion, metastasis, and tumor angiogenesis in HNSCC and that shows promise as an important therapeutic target in the treatment of HNSCC. In the current study, 72-hour honokiol treatments inhibited the growth of HNSCC cell lines, Cal-33, UM-22b and 1483 with IC50’s ranging from 3.90-7.44 μM, as shown through trypan blue dye exclusion assays. Honokiol treatment also decreased expression levels of phosphotyrosine STAT3 in these same cell lines. The growth inhibitory activity of honokiol is associated with apoptosis, as demonstrated by staining for annexin-V. Because clinical data indicates that currently available HNSCC therapies have been inadequate in improving mortality rates over the last three decades, it is of interest that honokiol enhances the activity of the small-molecule receptor tyrosine kinase inhibitor, erlotinib, in HNSCC cells. Finally, honokiol was found to modestly inhibit the growth of tumors in HNSCC xenograft models. These results suggest that honokiol inhibits HNSCC growth in conjunction with downregulation of phosphotyrosine STAT3 in HNSCC.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):A134.