Effects of the tropical ginger compound,1’-acetoxychavicol acetate, against tumor promotion in K5.Stat3C transgenic mice

Journal of Experimental & Clinical Cancer Research

Heather E Kleiner-Hancock³  John L Clifford³  Runhua Shi¹  J Michael Mathis³  John DiGiovanni²  Patrick Adegboyega³  Malari A Coburn³  Jennifer N Gill³  Zanobia Syed³  Vinita Batra³ 

[1] Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA;School of Human Ecology, University of Texas, Austin, TX, USA;Feist-Weiller Cancer Center, Shreveport, LA, USA

关键词: Tropical ginger;    TPA;    Carcinogenesis;    Squamous cell carcinoma;    Stat3;    NF-κB;   

Others  :  826305
DOI  :  10.1186/1756-9966-31-57

 received in 2012-02-16, accepted in 2012-06-02,  发布年份 2012

【 摘 要 】

The purpose of the current study was to determine whether a tropical ginger derived compound 1’-acetoxychavicol acetate (ACA), suppresses skin tumor promotion in K5.Stat3C mice. In a two-week study in which wild-type (WT) and K5.Stat3C mice were co-treated with either vehicle, ACA, galanga extract, or fluocinolone acetonide (FA) and tetradecanoyl phorbol acetate (TPA), only the galanga extract and FA suppressed TPA-induced skin hyperproliferation and wet weight. None of these agents were effective at suppressing p-Tyr⁷⁰⁵Stat3 expression. However, ACA and FA showed promising inhibitory effects against skin tumorigenesis in K5.Stat3C mice. ACA also suppressed phospho-p65 NF-κB activation, suggesting a potential mechanism for its action.

【 授权许可】

   
2012 Batra et al. licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Baade PD, Balanda KP, Lowe JB: Changes in skin protection behaviors, attitudes, and sunburn: in a population with the highest incidence of skin cancer in the world. Cancer Detect Prev 1996, 20:566-575.
• [2]Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin 2010, 60:277-300.
• [3]DiGiovanni J: Multistage carcinogenesis in mouse skin. Pharmacol Ther 1992, 54:63-128.
• [4]Boutwell RK: Some Biological Aspects of Skin Carcinogenisis. Prog Exp Tumor Res 1964, 4:207-250.
• [5]Slaga TJ, Fischer SM, Nelson K, Gleason GL: Studies on the mechanism of skin tumor promotion: evidence for several stages in promotion. Proc Natl Acad Sci USA 1980, 77:3659-3663.
• [6]Boutwell RK: The function and mechanism of promoters of carcinogenesis. CRC Crit Rev Toxicol 1974, 2:419-443.
• [7]Yuspa SH, Poirier MC: Chemical carcinogenesis: from animal models to molecular models in one decade. Adv Cancer Res 1988, 50:25-70.
• [8]Chan KS, Carbajal S, Kiguchi K, Clifford J, Sano S, DiGiovanni J: Epidermal growth factor receptor-mediated activation of Stat3 during multistage skin carcinogenesis. Cancer Res 2004, 64:2382-2389.
• [9]Ihle JN: The Stat family in cytokine signaling. Curr Opin Cell Biol 2001, 13:211-217.
• [10]Chan KS, Sano S, Kiguchi K, Anders J, Komazawa N, Takeda J, DiGiovanni J: Disruption of Stat3 reveals a critical role in both the initiation and the promotion stages of epithelial carcinogenesis. J Clin Invest 2004, 114:720-728.
• [11]Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, Itami S, Nickoloff BJ, DiGiovanni J: Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 2005, 11:43-49.
• [12]Sano S, Chan KS, Kira M, Kataoka K, Takagi S, Tarutani M, Itami S, Kiguchi K, Yokoi M, Sugasawa K, Mori T, Hanaoka F, Takeda J, DiGiovanni J: Signal transducer and activator of transcription 3 is a key regulator of keratinocyte survival and proliferation following UV irradiation. Cancer Res 2005, 65:5720-5729.
• [13]Yin W, Cheepala S, Roberts JN, Syson-Chan K, DiGiovanni J, Clifford JL: Active Stat3 is required for survival of human squamous cell carcinoma cells in serum-free conditions. Mol Cancer 2006, 5:15. BioMed Central Full Text
• [14]Kataoka K, Kim DJ, Carbajal S, Clifford J, DiGiovanni J: Stage-specific disruption of Stat3 demonstrates a direct requirement during both the initiation and promotion stages of mouse skin tumorigenesis. Carcinogenesis 2008, 29:1108-1114.
• [15]Syed Z, Cheepala SB, Gill JN, Stein J, Nathan CA, Digiovanni J, Batra V, Adegboyega P, Kleiner HE, Clifford JL: All-trans retinoic acid suppresses Stat3 signaling during skin carcinogenesis. Cancer Prev Res (Phila Pa) 2009, 2:903-911.
• [16]Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell JE Jr: Stat3 as an oncogene. Cell 1999, 98:295-303.
• [17]Chan KS, Sano S, Kataoka K, Abel E, Carbajal S, Beltran L, Clifford J, Peavey M, Shen J, Digiovanni J: Forced expression of a constitutively active form of Stat3 in mouse epidermis enhances malignant progression of skin tumors induced by two-stage carcinogenesis. Oncogene 2008, 27:1087-1094.
• [18]Karin M: Nuclear factor-kappaB in cancer development and progression. Nature 2006, 441:431-436.
• [19]Aggarwal S, Takada Y, Singh S, Myers JN, Aggarwal BB: Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-kappaB signaling. Int J Cancer 2004, 111:679-692.
• [20]Loercher A, Lee TL, Ricker JL, Howard A, Geoghegen J, Chen Z, Sunwoo JB, Sitcheran R, Chuang EY, Mitchell JB, Baldwin AS Jr, Van Waes C: Nuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma. Cancer Res 2004, 64:6511-6523.
• [21]Kobielak A, Fuchs E: Links between alpha-catenin, NF-kappaB, and squamous cell carcinoma in skin. Proc Natl Acad Sci USA 2006, 103:2322-2327.
• [22]Mukhtar H, Agarwal R: Skin cancer chemoprevention. J Investig Dermatol Symp Proc 1996, 1:209-214.
• [23]Gupta S, Mukhtar H: Chemoprevention of skin cancer: current status and future prospects. Cancer Metastasis Rev 2002, 21:363-380.
• [24]Bickers DR, Athar M: Novel approaches to chemoprevention of skin cancer. J Dermatol 2000, 27:691-695.
• [25]Kondo A, Ohigashi H, Murakami A, Suratwadee J, Koshimizu K: 1'-Acetoxychavicol Acetate as a Potent inhibitor of Tumor Promoter-induced Epstein-Barre Virus Activation from Languas galanga, a Traditional Thai Condiment. Biosci. Biotech. Biochem 1993, 57:1344-1345.
• [26]Murakami A, Kuki W, Takahashi Y, Yonei H, Nakamura Y, Ohto Y, Ohigashi H, Koshimizu K: Auraptene, a citrus coumarin, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in ICR mouse skin, possibly through suppression of superoxide generation in leukocytes. Jpn J Cancer Res 1997, 88:443-452.
• [27]Murakami A, Ohura S, Nakamura Y, Koshimizu K, Ohigashi H: 1'-Acetoxychavicol acetate, a superoxide anion generation inhibitor, potently inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in ICR mouse skin. Oncology 1996, 53:386-391.
• [28]Tanaka T, Kawabata K, Kakumoto M, Matsunaga K, Mori H, Murakami A, Kuki W, Takahashi Y, Yonei H, Satoh K, Hara A, Maeda M, Ota T, Odashima S, Koshimizu K, Ohigashi H: Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by citrus auraptene in rats. Carcinogenesis 1998, 19:425-431.
• [29]Ohnishi M, Tanaka T, Makita H, Kawamori T, Mori H, Satoh K, Hara A, Murakami A, Ohigashi H, Koshimizu K: Chemopreventive effect of a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate, on rat oral carcinogenesis. Jpn J Cancer Res 1996, 87:349-356.
• [30]Tanaka T, Kawabata K, Kakumoto M, Makita H, Matsunaga K, Mori H, Satoh K, Hara A, Murakami A, Koshimizu K, Ohigashi H: Chemoprevention of azoxymethane-induced rat colon carcinogenesis by a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate. Jpn J Cancer Res 1997, 88:821-830.
• [31]Tanaka T, Kawabata K, Kakumoto M, Hara A, Murakami A, Kuki W, Takahashi Y, Yonei H, Maeda M, Ota T, Odashima S, Yamane T, Koshimizu K, Ohigashi H: Citrus auraptene exerts dose-dependent chemopreventive activity in rat large bowel tumorigenesis: the inhibition correlates with suppression of cell proliferation and lipid peroxidation and with induction of phase II drug-metabolizing enzymes. Cancer Res 1998, 58:2550-2556.
• [32]Ito K, Nakazato T, Murakami A, Yamato K, Miyakawa Y, Yamada T, Hozumi N, Ohigashi H, Ikeda Y, Kizaki M: Induction of apoptosis in human myeloid leukemic cells by 1'-acetoxychavicol acetate through a mitochondrial- and Fas-mediated dual mechanism. Clin Cancer Res 2004, 10:2120-2130.
• [33]Moffatt J, Hashimoto M, Kojima A, Kennedy DO, Murakami A, Koshimizu K, Ohigashi H, Matsui-Yuasa I: Apoptosis induced by 1'-acetoxychavicol acetate in Ehrlich ascites tumor cells is associated with modulation of polyamine metabolism and caspase-3 activation. Carcinogenesis 2000, 21:2151-2157.
• [34]Kawabata K, Tanaka T, Yamamoto T, Ushida J, Hara A, Murakami A, Koshimizu K, Ohigashi H, Stoner GD, Mori H: Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate. Jpn J Cancer Res 2000, 91:148-155.
• [35]Nakamura Y, Murakami A, Ohto Y, Torikai K, Tanaka T, Ohigashi H: Suppression of tumor promoter-induced oxidative stress and inflammatory responses in mouse skin by a superoxide generation inhibitor 1'-acetoxychavicol acetate. Cancer Res 1998, 58:4832-4839.
• [36]Campbell CT, Prince M, Landry GM, Kha V, Kleiner HE: Pro-apoptotic effects of 1'-acetoxychavicol acetate in human breast carcinoma cells. Toxicol Lett 2007, 173:151-160.
• [37]Ichikawa H, Takada Y, Murakami A, Aggarwal BB: Identification of a novel blocker of I kappa B alpha kinase that enhances cellular apoptosis and inhibits cellular invasion through suppression of NF-kappa B-regulated gene products. J Immunol 2005, 174:7383-7392.
• [38]Batra: Effects of chemopreventive agents in 12-O-tetradecanoylphorbol-13-acetate (TPA) treated mouse epidermis. Louisiana State University-Health Sciences Center, Shreveport, Shreveport; 2007:191. Pharmacology, Toxicology & Neuroscience
• [39]Li Y, Wheeler DL, Alters W, Chaiswing L, Verma AK, Oberley TD: Early epidermal destruction with subsequent epidermal hyperplasia is a unique feature of the papilloma-independent squamous cell carcinoma phenotype in PKCepsilon overexpressing transgenic mice. Toxicol Pathol 2005, 33:684-694.
• [40]Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976, 72:248-254.
• [41]Stanley PL, Steiner S, Havens M, Tramposch KM: Mouse skin inflammation induced by multiple topical applications of 12-O-tetradecanoylphorbol-13-acetate. Skin Pharmacol 1991, 4:262-271.
• [42]Aziz MH, Manoharan HT, Verma AK: Protein kinase C epsilon, which sensitizes skin to sun's UV radiation-induced cutaneous damage and development of squamous cell carcinomas, associates with Stat3. Cancer Res 2007, 67:1385-1394.
• [43]Murakami A, Toyota K, Ohura S, Koshimizu K, Ohigashi H: Structure-activity relationships of (1'S)-1'-acetoxychavicol acetate, a major constituent of a southeast Asian condiment plant Languas galanga, on the inhibition of tumor-promoter-induced Epstein-Barr virus activation. J Agric Food Chem 2000, 48:1518-1523.
• [44]Sporn MB, Dunlop NM, Newton DL, Smith JM: Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc 1976, 35:1332-1338.
• [45]Schwarz JA, Viaje A, Slaga TJ: Fluocinolone acetonide: a potent inhibitor of mouse skin tumor promotion and epidermal DNA synthesis. Chem Biol Interact 1977, 17:331-347.
• [46]Kleiner-Hancock HE, Shi R, Remeika A, Robbins D, Prince M, Gill JN, Syed Z, Adegboyega P, Mathis JM, Clifford JL: Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts. BMC Cancer 2010, 10:394. BioMed Central Full Text
• [47]Cheepala SB, Yin W, Syed Z, Gill JN, McMillian A, Kleiner HE, Lynch M, Loganantharaj R, Trutschl M, Cvek U, Clifford JL: Identification of the B-Raf/Mek/Erk MAP kinase pathway as a target for all-trans retinoic acid during skin cancer promotion. Mol Cancer 2009, 8:27. BioMed Central Full Text