Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-unsaturated carbonyl group is a prerequisite.

Abstract

Zerumbone (ZER), a sesquiterpene from the edible plant Zingiber zerumbet Smith, has recently been found to suppress tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in a potent manner. In the present study, we evaluated the anti-inflammatory and chemopreventive potentials of ZER in a variety of cell culture experiments. ZER effectively suppressed TPA-induced superoxide anion generation from both NADPH oxidase in dimethylsulfoxide-differentiated HL-60 human acute promyelocytic leukemia cells and xanthine oxidase in AS52 Chinese hamster ovary cells. The combined lipopolysaccharide- and interferon-gamma-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2, together with the release of tumor necrosis factor-alpha, in RAW 264.7 mouse macrophages were also markedly diminished. These suppressive events were accompanied with a combined decrease in the medium concentrations of nitrite and prostaglandin E(2), while the expression level of COX-1 was unchanged. ZER inhibited the proliferation of human colonic adenocarcinoma cell lines (LS174T, LS180, COLO205, and COLO320DM) in a dose-dependent manner, while the growth of normal human dermal (2F0-C25) and colon (CCD-18 Co) fibroblasts was less affected. It also induced apoptosis in COLO205 cells, as detected by dysfunction of the mitochondria transmembrane, Annexin V-detected translocation of phosphatidylserine, and chromatin condensation. Intriguingly, alpha-humulene, a structural analog lacking only the carbonyl group in ZER, was virtually inactive in all experiments conducted, indicating that the alpha,beta-unsaturated carbonyl group in ZER may play some pivotal roles in interactions with unidentified target molecule(s). Taken together, our results indicate that ZER is a food phytochemical that has distinct potentials for use in anti-inflammation, chemoprevention, and chemotherapy strategies.

• Authors: Akira Murakami, Daisuke Takahashi, Takashi Kinoshita, Koichi Koshimizu, Ha Won Kim, Akira Yoshihiro, Yoshimasa Nakamura, Suratwadee Jiwajinda, Junji Terao, Hajime Ohigashi
• Journal: Carcinogenesis (Carcinogenesis) Vol. 23 Issue 5 Pg. 795-802 (May 2002) ISSN: 0143-3334 [Print] England
• PMID: 12016152 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Free Radicals
• Isoenzymes
• Membrane Proteins
• Sesquiterpenes
• Tumor Necrosis Factor-alpha
• Superoxides
• zerumbone
• NOS2 protein, human
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• Tetradecanoylphorbol Acetate

Topics

• Adenocarcinoma (metabolism, pathology)
• Animals
• Anticarcinogenic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Division (drug effects)
• Colonic Neoplasms (metabolism, pathology)
• Cyclooxygenase 2
• Free Radicals
• Humans
• Isoenzymes (metabolism)
• Membrane Proteins
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type II
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Sesquiterpenes (pharmacology)
• Superoxides (metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, metabolism)