Summary
Gallates with eight or more carbon atoms in the lateral chain show potent anticancer activity against various cell lines. However, studies regarding the in vivo antimelanoma activity of tetradecyl gallate (C14) have not yet been reported. In this study an evaluation of the ability of C14 to inhibit metastasis, using lung metastases as a model, was carried out. The experimental mouse melanoma model was established by intravenous injection of metastatic B16F10 melanoma cells. The systemic toxicity of C14 was evaluated in vivo by monitoring the weight, survival, biochemical and hematological parameters, and through histological analysis. It was observed that C14 decreased lung metastasis in vivo by 80% and increased the survival rate of the animals without toxic effects. Additionally, C14 induced cytotoxic effects on B16F10 cells, inhibited the inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, and significantly decreased cell adhesion. These results reveal that C14 has potent antimetastatic ability and is a good candidate for further study as a potential therapeutic agent for tumor metastases.
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Saleem A, Husheem M, Härkönen P, Pihlaja K (2002) Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit. J Ethnopharmacol 81(3):327–36
Zhang S, Li M, Gu Y, Liu Z, Xu S, Cui Y, Sun B (2008) Thalidomide influences growth and vasculogenic mimicry channel formation in melanoma. J Exp Clin Cancer Res 27(60) doi: 10.1186/1756-9966-27-60
Veluri R, Singh RP, Liu Z, Thompson JA, Agarwal R, Agarwal C (2006) Fraction of grape seed extract and identification of gallic acid as one of the major active constituents causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells. Carcinogenesis 27:1445–1453
Lansky EP, Newman RA (2007) Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 109(2):177–206
Silva SL, Chaar JS, Yano T (2009) Chemotherapeutic potential of two gallic acid derivative compounds from leaves of Casearia sylvestris Sw (Flacourtiaceae). Eur J Pharm 608:76–83
Kang MS, Oh JS, Kang IC, Hong SJ, Choi CH (2008) Inhibitory effect of methyl gallate and gallic acid on oral bacteria. J Microbiol 46:744–750
Giftson JS, Jayanthi S, Nalini N (2010) Chemopreventive efficacy of gallic acid an antioxidant and anticarcinogenic polyphenol, against 1, 2-dimethyl hydrazine induced rat colon carcinogenesis. Invest New Drugs 28(3):251–259
Savi LA, Leal PC, Vieira TO, Rosso R, Nunes RJ, Yunes RA, Creczynski-Pasa TB, Barardi CRM, Simões CMO (2005) Evaluation of anti-herpetic and antioxidant activities, and cytotoxic and genotoxic effects the synthetic alkyl-esters of gallic acid. Arzneimittelforschung 55:66–75
Rosso R, Vieira TO, Leal PC, Nunes RJ, Yunes RA, Creczynski-Pasa TB (2006) Relationship between the lipophilicity of gallic acid n-alquil esters’ derivatives and both myeloperoxidase activity and HOCl scavenging. Bioorg Med Chem 14(18):6409–13
Locatelli C, Rosso R, Santos-Silva MC, Souza CA, Licínio MA, Leal PC, Bazzo ML, Yunes RA, Creczynski-Pasa TB (2008) Ester derivatives of gallic acid with potential toxicity toward L1210 leukemia cells. Bioorg Med Chem 16:3791–3799
Locatelli C, Leal PC, Yunes RA, Nunes RJ, Creczynski-Pasa TB (2009) Gallic acid ester derivatives induce apoptosis and cell adhesion inhibition in melanoma cells: the relationship between free radical generation, glutathione depletion and cell death. Chem Biol Interact 181:175–184
Gava B, Zorzet S, Spessotto P, Cocchietto M, Sava G (2006) Inhibition of B16 melanoma metastases with the ruthenium complex imidazolium trans-imidazoledimethylsulfoxide-tetrachlororuthenate and down-regulation of tumor cell invasion. J Pharmacol Exp Ther 317:284–291
Maruta S, Takiguchi S, Ueyama M, Kataoka Y, Oda Y, Tsuneyoshi M, Iguchi H (2008) A role leukemia inhibitory factor in melanoma-induced bone metastasis. Clin Exp Metastasis 26(2):133–141
Flores FF, Pardi PC, Santos RP, Rando DG, Pablo JA, Suárez Q, Maria DA (2008) Antiproliferative and antimetastatic of DM-1, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1, 4-dienyl]-2-methoxy-phenolate, in B16F10 melanoma. Appl Cancer Res 28(2):72–79
Balch CM, Soong SJ, Atkins MB, Buzaid AC, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A Jr, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF (2004) An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin 54:131–149
Ebrahimnejad A, Streichert T, Nollau P, Horst AK, Wagener C, Bamberger AM, Brümmer J (2004) CEACAM1 enhances invasion and migration of melanocytic and melanoma cells. Am J Pathol 165(5):1781–1787
Haass NK, Smalley KSM, Li L, Herlyn M (2005) Adhesion, migration and communication in melanocytes and melanoma. Pigment Cell Res 18:150–159
Van der Heijden CA, Janssen PJ, Strik JJ (1986) Toxicology of gallates: a review and evaluation. Food Chem Toxicol 24:1067–1070
Lu Z, Nie G, Belton PS, Tang H, Zhao B (2006) Structure-activity relationship analysis of antioxidant ability and neuroprotective effect of gallic acid derivatives. Neurochem Int 48:263–274
Van De Loosdrecht AA, Nennie E, Ossenkoppele GJ, Beelen RH, Langenhuijsen MM (1991) Cell mediated cytotoxicity against U 937 cells by human monocytes and macrophages in a modified colorimetric MTT assay. A methodological study J Immunol Meth 141(1):15–22
Mené P, Fais S, Cinotti GA, Pugliese F, Luttmann W, Thierauch K-H (1995) Regulation of U937 monocyte adhesion to cultured human mesangial cells by cytokines and vasoactive agents. Nephrol Dial Transplant 10:481–489
Kornberg L, Earp S, Parsons JT, Schaller M, Juliano RL (1992) Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion associated tyrosine kinase. J Biol Chem 267:23439–23442
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Cos P, Calomme M, Sindambiwe JB, De Bruyne T, Cimanga K, Pieters L, Vlietinck AJ, Vanden Berghe D (2001) Cytotoxicity and lipid peroxidation-inhibiting activity of flavonoids. Planta Med 67(6):515–519
Cos P, Rajan P, Vedernikova I, Calomme M, Pieters L, Vlietinck AJ, Augustyns K, Haemers A, Vanden Berghe D (2002) In vitro antioxidant profile of phenolic acid derivatives. Free Radic Res 36(6):711–716
Parhar RS, Lala PK (1987) Ameliortion of B16F10 melanoma lungs metastasis in mice by a combination therapy with indomethacin and interleukin-2. J Exp Med 165:14–28
Garg DK, Goyal RN (1992) Haematological and hepatotoxic effects of silken styles of corn in albino rats. J Appl Toxicol 12(5):359–363
Pari L, Murugavel P (2005) Role of diallyl tetrasulfide in ameliorating the cadmium induced biochemical changes in rats. Envir Toxicol Pharmacol 20:493–500
Ellman GL (1959) Tissue sulphydryl groups. Arch Biochem Biophys 82:70–77
Ohkawa H, Ohishi H, Yagi K (1979) Assay for lipid peroxide in animal tissue by thiobarbituric acid reaction. Anal Biochem 95:351–358
Yamaguchi H, Kitayama J, Takuwa N, Arikawa K, Inoki I, Takehara K, Nagawa H, Takuwa Y (2003) Sphingoine-1-phosphate receptor subtype-specific positive and negative regulation of Rac and haematogenous metastasis of melanoma cells. J Biochem 374:715–722
Mckinnon JG, Yu XQ, McCarthy WH, Thompson JF (2003) Prognosis for patients with thin cutaneous melanoma: long-term survival data from New South Wales Central Registry and the Sydney Melanoma Unit. Cancer 98(6):1223–1231
Zell JA, Cinar P, Mobasher M, Ziogas A, Meyskens FL, Jr Anton-Culver H (2008) Survival for patients with invasive cutaneous melanoma among ethnic groups: the effects of socioeconomic status and treatment. J Clin Oncol 26(1):66–75
Bai RZ, Wu Y, Liu Q, Xie K, Wei YQ, Wang YS, Liu K, Luo Y, Su JM, Hu B, Liu JY, Li Q, Niu T, Zhao W, Yang L (2009) Suppression of lung cancer in murine model: treated by combination of recombinant human endostsatin adenovirus with low-dose cisplatin. J Exp Clin Cancer Res 28(31):1–9
Sirohi B, Smith K (2008) Bevacizumab in the treatment of breast cancer. Expert Rev Anticancer Ther 8:1559–1568
Wang Y, Zhou B, Li J, Cao YB, Chen XS, Cheng MH, Yin M (2004) Inhibitors of 5-lipoxyenase inhibit expression of intercellular adhesion molecule-1 in human melanoma cells. Acta Pharmacol Sin 25:672–677
Yao Z, Che X, Lu R, Zheng M, Zhu Z, Li J, Jian X, Shi L, Liu J, Gao W (2007) Inhibition by tyroserleutide (YSL) on the invasion and adhesion of the mouse melanoma cell. Mol Med 13(1–2):14–21
Johnson JP (1999) Cell adhesion molecules in the development and progression of malignant melanoma. Cancer Metastasis Rev 18:345–357
Woo CH, Lim JH, Kim JH (2005) VCAM-1 upregulation via PKCdelta-p38 kinase-linked cascade mediates the TNF-alpha-induced leukocyte adhesion and emigration in the lung airway epithelium. Am J Physiol Lung Cell Mol Physiol 288(2):L307–L316
Sun W, Schuchter LM (2001) Metastatic melanoma. Curr Treat Options Oncol 2:193–202
Shimamoto T, Tomoda A, Ishida R, Ohyashiki K (2001) Antitumor effects of a novel phenoxazine derivative on human leukemia cell lines in vitro and in vivo. Clin Cancer Res 7:704–708
Acknowledgments
This study was supported by grants from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), FAPESC (Fundação de Amparo à Pesquisa de Santa Catarina) and a fellowship from the Universidade do Contestado. This article forms part of the PhD research of Claudriana Locatelli and of Clarissa A. S. de Cordova of the Pharmacy post-graduation course. The research group would also like to thank the Hospital Universitário (HU) for the use of their facilities.
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Locatelli, C., Carvalho, D.R., Mascarello, A. et al. Antimetastatic activity and low systemic toxicity of tetradecyl gallate in a preclinical melanoma mouse model. Invest New Drugs 30, 870–879 (2012). https://doi.org/10.1007/s10637-010-9628-7
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DOI: https://doi.org/10.1007/s10637-010-9628-7