Vanillin enhances TRAIL-induced apoptosis in cancer cells through inhibition of NF-kappaB activation.
BACKGROUND
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent which selectively kills cancer cells with little effect on normal cells. However, TRAIL resistance is widely found in cancer cells. We have previously reported antimetatstatic and antiangiogenic effects of vanillin, a flavoring agent from vanilla. Here we have evaluated the sensitizing effect of vanillin on a TRAIL-resistant human cervical cancer cell line, HeLa.


METHODS
Cell viability after treatments was determined by the WST-1 cell counting kit. Apoptosis was demonstrated by detection of caspase-3 activation and cleavage of poly (ADP-ribose) polymerase using immunoblot analysis. Effect of treatments on TRAIL signaling pathway and nuclear factor kappaB (FN-kappaB) activation was studied using immunoblot analysis and luciferase reporter assay.


RESULTS
Pretreatment of HeLa cells with vanillin enhanced TRAIL-induced cell death through the apoptosis pathway. Vanillin pretreatment inhibited TRAIL-induced phosphorylation of p65 and transcriptional activity of NF-kappaB.


CONCLUSIONS
Vanillin sensitizes HeLa cells to TRAIL-induced apoptosis by inhibiting NF-kappaB activation.
Lirdprapamongkol
Kriengsak
K
Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.
Sakurai
Hiroaki
H
Suzuki
Shunsuke
S
Koizumi
Keiichi
K
Prangsaengtong
Orawin
O
Viriyaroj
Amornrat
A
Ruchirawat
Somsak
S
Svasti
Jisnuson
J
Saiki
Ikuo
I
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D001547:Benzaldehydes / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D017930:Genes, Reporter; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D009369:Neoplasms / Q000473:pathology*; D010766:Phosphorylation; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology
D000975:Antioxidants; D001547:Benzaldehydes; D016328:NF-kappa B; D053221:TNF-Related Apoptosis-Inducing Ligand; C100058:vanillin; D008156:Luciferases