Induction of Laryngeal Cancer Cell Death by Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic Acid.

Background. Ent-11-hydroxy-15-oxo-kaur-16-en-19-oic acid (5F) is known to exhibit antitumor activity, but its mechanism is not completely understood. 5F has not been tested in laryngeal cancer.Methods. Two laryngeal cancer cell lines were treated with 5F. Cell death was analyzed by MTT [3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide] and Annexin V assay. Nuclear factor kappa beta (NE-kappa B)- and apoptosis-related molecules were examined.Results. 5F induced laryngeal cancer cell death in a dosedependent manner. The Annexin V assay and the measurement of cleavage of procaspase-3 and poly(ADP-ribose) polymerase demonstrated that the 5F-induced cell death was mainly apoptotic. 5F slightly reduced the basal level of NF-kappa B, but significantly suppressed the inducible NE-kappa B by reducing its transcriptional activity, protecting its inhibitory subunit IKB alpha from degradation, and suppressing its level in the nucleus. also inhibited pro-proliferative and anti-apoptotic molecules but promoted pro-apoptotic Bax.Conclusions. 5F induces apoptosis of laryngeal cancer cells by inhibiting NE-kappa B activation/induction, suppressing pro-proliferative and anti-apoptotic molecules, and promoting pro-apoptotic Bax. (C) 2010 Wiley Periodicals, Inc. Head Neck 32: 1506-1518, 2010