Planta Med 2004; 70(8): 723-727
DOI: 10.1055/s-2004-827202
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

An ent-Kaurene Diterpene Enhances Apoptosis Induced by Tumor Necrosis Factor in Human Leukemia Cells

Ikue Suzuki1 , Masuo Kondoh1 , Motoki Harada1 , Naoya Koizumi1 , Makiko Fujii1 , Fumihiro Nagashima2 , Yoshinori Asakawa2 , Yoshiteru Watanabe1
  • 1Department of Pharmaceutics and Biopharmaceutics, Showa Pharmaceutical University, Tokyo, Japan
  • 2Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan
Further Information

Publication History

Received: January 28, 2004

Accepted: May 8, 2004

Publication Date:
24 August 2004 (online)

Abstract

Some antitumor agents, including tumor necrosis factor-α (TNF-α) and camptothecin (CPT), often cause resistance of tumor cells to antitumor agents through activation of the nuclear factor-κB (NF-κB) pathway that leads to up-regulation of anti-apoptotic proteins. Therefore, co-treatment of an inhibitor of the NF-κB pathway with antitumor agents is a useful strategy for chemotherapy. Here we report that ent-11α-hydroxy-16-kauren-15-one (KD) selectively inhibits NF-κB-dependent gene expression due to treatment with TNF-α. KD in combination with TNF-α caused a dramatic increase in apoptosis in human leukemia cells accompanied by activation of caspases. A broad-spectrum inhibitor of caspases decreased the apoptosis induced by treatment with KD and TNF-α. KD in combination with CPT also caused an increase in apoptosis. These results suggest that the apoptotic potency of co-treatment of KD with TNF-α or CPT is elicited through selective inhibition of NF-κB-dependent anti-apoptotic proteins and thus may provide a basis for the development of useful approaches to the treatment of leukemia.

Abbreviations

NF-κB:nuclear factor-κB

KD:ent-11α-hydroxy-16-kauren-15-one

PARP:poly (ADP-ribose) polymerase

TNF-α:tumor necrosis factor-α

CPT:camptothecin

IAPs:inhibitor of apoptosis proteins

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Dr. Masuo Kondoh

Department of Pharmaceutics and Biopharmaceutics

Showa Pharmaceutical University

Machida

Tokyo 194-8543

Japan

Phone: +81-42-721-1556

Fax: +81-42-721-3585

Email: masuo@ac.shoyaku.ac.jp