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 (NF-κB)- and apoptosis-related molecules were examined.


RESULTS
5F induced laryngeal cancer cell death in a dose-dependent 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-κB, but significantly suppressed the inducible NF-κB by reducing its transcriptional activity, protecting its inhibitory subunit IκBα from degradation, and suppressing its level in the nucleus. 5F also inhibited pro-proliferative and anti-apoptotic molecules but promoted pro-apoptotic Bax.


CONCLUSIONS
5F induces apoptosis of laryngeal cancer cells by inhibiting NF-κB activation/induction, suppressing pro-proliferative and anti-apoptotic molecules, and promoting pro-apoptotic Bax.
Department of Otorhinolaryngology-Head and Neck Surgery, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. lexvlantis@cuhk.edu.hk
Alexander C
AC
Vlantis
Chun Shan
CS
Lo
George G
GG
Chen
Nian
N
Ci Liang
Vivian W Y
VW
Lui
Kefeng
K
Wu
Yi Feng
YF
Deng
Xianling
X
Gong
Yingnian
Y
Lu
Michael C F
MC
Tong
C Andrew
CA
van Hasselt
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000187:drug effects; D051034:Inhibitor of Apoptosis Proteins; D007822:Laryngeal Neoplasms / Q000473:pathology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000077022:Survivin; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C479310:11-hydroxy-15-oxokaur-16-en-19-olic acid; C494826:BAX protein, human; C107489:BIRC5 protein, human; C530104:CCND1 protein, human; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D000077022:Survivin; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011065:Poly(ADP-ribose) Polymerases; C512478:EGFR protein, human; D066246:ErbB Receptors; D051550:I-kappa B Kinase; D053148:Caspase 3