Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice

Murakami, Akira; Tanaka, Takuji; Lee, Ji Yoon; Surh, Young Joon; Kim, Ha Won; Kawabata, Kyuichi; Nakamura, Yoshimasa; Jiwajinda, Suratwadee; Ohigashi, Hajime

doi:10.1002/ijc.20175

Cited by 153 publications

(107 citation statements)

References 66 publications

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“…Abundance of phytochemicals have been investigated and evidenced to be a promising chemopreventive agent. Eugenol, resveratrol, zerumbone and zapotin are among reported phytochemicals which warrants further investigation as chemopreventive agents attributable to their anti-tumor effects during initiation, promotion, or a combination of both stages (Murakami et al, 2004;Cuendet et al, 2008;Kalra et al, 2008;Pal et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

Yeong

Hamid²,

Yazan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(α)anthracene (DMBA, 100 µg/100 µl) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/ promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume (8.79±5.44) and tumor burden (3.60±1.17). Comparatively, group III revealed only 20% of tumor incidence, tumor burden (3.00±1.00) and tumor volume (2.40±1.12), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

Yeong

Hamid²,

Yazan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…The researchers also observed that zerumbone lowered the levels of inflammatory biomarkers IL1b, TNF-a and prostaglandin E2 in the mouse colonic mucosa. In a subsequent paper Murakami and co-workers reported suppressive effect of zerumbone on 7,12-dimethylbenz[a]anthracene-and TPA-induced initiation and promotion of skin tumors in ICR mice [66]. Topical application of zerumbone was found to enhance mRNA expression levels of anti-oxidative and phase II xenobiotic metabolizing enzymes manganese superoxide dismutase (MnSOD), glutathione peroxidise-1 (GPx-1), GST-P1 and NQO1 in the mouse epidermis.…”

Section: In Vivo Anti-cancer Effects Of Zerumbonementioning

confidence: 95%

Key cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer

Prasannan

Kalesh

Shanmugam

et al. 2012

Biochemical Pharmacology

128

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“…Our pervious study revealed that topical application of zerumbone inhibited chemically induced mouse skin papillomagenesis (19). This prompted us to examine whether zerumbone could induce HO-1 expression in mouse skin in vivo.…”

Section: Involvement Of Nrf2-are In Zerumbone-induced Expression Of Hmentioning

confidence: 99%

“…Numerous phytochemicals exert chemopreventive effects through induction of phase 2 detoxifying enzymes and cytoprotective proteins. Zerumbone, a major sesquiterpene found in the rhizomes of Zingiber zerumbet Smith (Zingiberaceae), has been shown to have strong antioxidant (16), antiinflammatory (17), and anticarcinogenic (18,19) properties in several in vitro and in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

Zerumbone Induces Heme Oxygenase-1 Expression in Mouse Skin and Cultured Murine Epidermal Cells through Activation of Nrf2

Shin

Ohnishi

Murakami

et al. 2011

Cancer Prevention Research

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Zerumbone, a sesquiterpene derived from tropical ginger, contains an electrophilic a,b-unsaturated carbonyl moiety and was found to suppress chemically induced papilloma formation in mouse skin. Here, we report that topical application of zerumbone onto dorsal skin of hairless mice induces activation of NF-E2-related factor 2 (Nrf2) and expression of heme oxygenase-1 (HO-1). We compared the levels of HO-1 protein in the skin of zerumbone-treated Nrf2 wild-type and Nrf2 knockout mice, and nrf2-deficient mice expressed HO-1 protein to a much lesser extent than the wild-type animals following topical application of zerumbone. Treatment of mouse epidermal JB6 cells with zerumbone caused a marked increase of Nrf2 nuclear translocation followed by the promoter activity of HO-1, and also enhanced direct binding of Nrf2 to the antioxidant response element. Moreover, knockdown of Nrf2 in JB6 cells diminished the zerumbone-induced upregulation of HO-1. Notably, a-humulene and 8-hydroxy-a-humulene, the structural analogues of zerumbone that lack the a,b-unsaturated carbonyl group, failed to activate Nrf2 and were unable to increase HO-1 expression. Unlike zerumbone, these nonelectrophilic analogues could not suppress the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced JB6 cell transformation and the intracellular accumulation of reactive oxygen species (ROS). Interestingly, when JB6 cells were treated with carbon monoxide-releasing molecule that mimics the HO-1 activity, the TPA-induced ROS production was markedly reduced. Taken together, these findings suggest that upregulation of HO-1 expression by zerumbone is mediated through activation of Nrf2 signaling, which provides a mechanistic basis for the chemopreventive effects of this sesquiterpene on mouse skin carcinogenesis. Cancer Prev Res; 4(6); 860-70. Ó2011 AACR.

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Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice

Cited by 153 publications

References 66 publications

Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

Key cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer

Zerumbone Induces Heme Oxygenase-1 Expression in Mouse Skin and Cultured Murine Epidermal Cells through Activation of Nrf2

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