Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis

The α,β-unsaturated carbonyl group is a prerequisite

Akira Murakami, Daisuke Takahashi, Takashi Kinoshita, Koichi Koshimizu, Ha Won Kim, Akira Yoshihiro, Yoshimasa Nakamura, Suratwadee Jiwajinda, Junji Terao, Hajime Ohigashi

Research output: Contribution to journalArticle

249 Citations (Scopus)

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-γ-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2, together with the release of tumor necrosis factor-α, 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 E2, 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, α-humulene, a structural analog lacking only the carbonyl group in ZER, was virtually inactive in all experiments conducted, indicating that the α,β-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.

Original languageEnglish (US)
Pages (from-to)795-802
Number of pages8
JournalCarcinogenesis
Volume23
Issue number5
StatePublished - Jun 8 2002
Externally publishedYes

Fingerprint

Ginger
Sesquiterpenes
Free Radicals
Cell Proliferation
Apoptosis
Neoplasms
Proteins
Tetradecanoylphorbol Acetate
Virus Activation
Cyclooxygenase 1
Edible Plants
Acute Promyelocytic Leukemia
Xanthine Oxidase
NADPH Oxidase
Annexin A5
Phosphatidylserines
Chemoprevention
Phytochemicals
Nitric Oxide Synthase Type II
Cyclooxygenase 2

ASJC Scopus subject areas

  • Cancer Research

Cite this

Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis : The α,β-unsaturated carbonyl group is a prerequisite. / Murakami, Akira; Takahashi, Daisuke; Kinoshita, Takashi; Koshimizu, Koichi; Kim, Ha Won; Yoshihiro, Akira; Nakamura, Yoshimasa; Jiwajinda, Suratwadee; Terao, Junji; Ohigashi, Hajime.

In: Carcinogenesis, Vol. 23, No. 5, 08.06.2002, p. 795-802.

Research output: Contribution to journalArticle

Murakami, Akira ; Takahashi, Daisuke ; Kinoshita, Takashi ; Koshimizu, Koichi ; Kim, Ha Won ; Yoshihiro, Akira ; Nakamura, Yoshimasa ; Jiwajinda, Suratwadee ; Terao, Junji ; Ohigashi, Hajime. / Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis : The α,β-unsaturated carbonyl group is a prerequisite. In: Carcinogenesis. 2002 ; Vol. 23, No. 5. pp. 795-802.
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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-γ-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2, together with the release of tumor necrosis factor-α, 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 E2, 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, α-humulene, a structural analog lacking only the carbonyl group in ZER, was virtually inactive in all experiments conducted, indicating that the α,β-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.",
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T1 - Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis

T2 - The α,β-unsaturated carbonyl group is a prerequisite

AU - Murakami, Akira

AU - Takahashi, Daisuke

AU - Kinoshita, Takashi

AU - Koshimizu, Koichi

AU - Kim, Ha Won

AU - Yoshihiro, Akira

AU - Nakamura, Yoshimasa

AU - Jiwajinda, Suratwadee

AU - Terao, Junji

AU - Ohigashi, Hajime

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