Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human hepatocellular carcinoma cell lines via inhibition of NF kappa B.
OBJECTIVE
To investigate the reduction of cell viability in human hepatocellular carcinoma (HCC) cell lines induced by inhibition of nuclear factor kappa B (NF kappa B).


METHODS
HLE, SKHep1, and HepG2 were incubated and E3330 was used to compare the stimulation of some chemotherapeutic drugs with that of TNF family, Fas ligand, TNF alpha and TNF-related apoptosis-inducing ligand (TRAIL) at the point of the reduction of cell viability by inhibiting NF kappa B.


RESULTS
E3330 decreased NF kappa B levels in HLE cells stimulated by TNF and TRAIL. The cytotoxicity of the combination of TRAIL, TNF alpha, Fas ligand, and E3330 increased synergistically in a dose-dependent manner compared to either E3330 alone in all HCC cell lines by MTT assay. However, the combination of some chemotherapeutic drugs and E3330 did not decrease the cell viability.


CONCLUSIONS
Inhibition of NF kappa B sensitizes human HCC cell lines to TNF-mediated apoptosis including TRAIL, and TRAIL-based tumor therapy might be a powerful potential therapeutic tool in the treatment of human HCC.
Saitou
Yukiko
Y
First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
Shiraki
Katsuya
K
Yamanaka
Takenari
T
Miyashita
Kazumi
K
Inoue
Tomoko
T
Yamanaka
Yutaka
Y
Yamaguchi
Yumi
Y
Enokimura
Naoyuki
N
Yamamoto
Norihiko
N
Itou
Keiichi
K
Sugimoto
Kazushi
K
Nakano
Takeshi
T
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D016227:Benzoquinones / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D016227:Benzoquinones; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011422:Propionates; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C075569:E 3330