Liver Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2005; 11(40): 6258-6261
Published online Oct 28, 2005. doi: 10.3748/wjg.v11.i40.6258
Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human hepatocellular carcinoma cell lines via inhibition of NFκB
Yukiko Saitou, Katsuya Shiraki, Takenari Yamanaka, Kazumi Miyashita, Tomoko Inoue, Yutaka Yamanaka, Yumi Yamaguchi, Naoyuki Enokimura, Norihiko Yamamoto, Keiichi Itou, Kazushi Sugimoto, Takeshi Nakano
Yukiko Saitou, Katsuya Shiraki, Takenari Yamanaka, Kazumi Miyashita, Tomoko Inoue, Yutaka Yamanaka, Yumi Yamaguchi, Naoyuki Enokimura, Norihiko Yamamoto, Keiichi Itou, Kazushi Sugimoto, Takeshi Nakano, First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan
Author contributions: All authors contributed equally to the work.
Correspondence to: Katsuya Shiraki, MD, PhD, Assistant Professor, First Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. katsuyas@clin.medic.mie-u.ac.jp
Telephone: +81-59-231-5015 Fax: +81-59-231-5201
Received: August 26, 2004
Revised: October 4, 2004
Accepted: October 7, 2004
Published online: October 28, 2005
Abstract

AIM: To investigate the reduction of cell viability in human hepatocellular carcinoma (HCC) cell lines induced by inhibition of nuclear factor κB (NFκB).

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, TNFα and TNF-related apoptosis-inducing ligand (TRAIL) at the point of the reduction of cell viability by inhibiting NFκB.

RESULTS: E3330 decreased NFκB levels in HLE cells stimulated by TNF and TRAIL. The cytotoxicity of the combination of TRAIL, TNFα, 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.

CONCLUSION: Inhibition of NFκB 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.

Keywords: E3330, NFκB inhibitor, Cytotoxicity, TRAIL, TNFα, Fas ligand, Doxorubicin, Camptotecin