Original contributionA catechol antioxidant protocatechuic acid potentiates inflammatory leukocyte-derived oxidative stress in mouse skin via a tyrosinase bioactivation pathway
Introduction
Acute and chronic inflammatory states have been implicated as mediators of a number of pathological disorders including cancer. Chronic inflammation appears to be linked to tumorigenesis in the lung, the bowel, the bladder, the colon, and the skin. Although the mechanisms by which inflammatory cells show their carcinogenic effects remain unclear, some potential pathways have been proposed [1]. Inflammatory cells produce a highly complicated mixture of growth and differentiation cytokines as well as biologically active arachidonate metabolites. In addition, they possess the ability to generate and release a spectrum of reactive oxygen species (ROS) and free radicals during oxidative burst. Among inflammatory cells, polymorphonuclear leukocytes (PMNs) are particularly adept at generating and releasing ROS, including superoxide (O2−), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen (1O2) and hydroxyl radical (OH) [2], [3], [4]. The generation of O2− by PMNs is attributed to the activation of a plasma membrane NADPH oxidase. Utilization of O2−-derived H2O2 by myeloperoxidase (MPO) results in the formation of HOCl. Further reaction of HOCl with H2O2 generates 1O2. In addition, OH has been demonstrated to be generated from the interaction of HOCl with O2− [3]. Current evidence suggests that these ROS-derived inflammatory cells may be important in tumorigenesis. Recently we have reported that O2− from leukocytes plays an important role for continuous and excessive production of chemotactic factors, leading to chronic inflammation and hyperplasia in mouse skin [5], [6]. ROS production by double or multiple 12-O-tetradecanoylphorbol-13-acetate (TPA) treatments is closely associated with the metabolic activation of proximate carcinogens [7], [8] and the increased levels of oxidized DNA bases [9], [10], [11]. In the continuous studies on the antioxidative behavior of chemopreventive food factors in mouse skin [5], [6], [12], [13], [14], [15], [16], we have recently demonstrated that a potent inhibitor of leukocyte-derived ROS generation [5], [12], [13] effectively suppressed inflammation-related carcinogenesis [17], [18], [19], [20], [21], [22]. Thus, the regulation of ROS from activated leukocytes is proposed to be one of the most promising strategies for cancer control [16].
The simple phenolic protocatechuic acid (PA) is one of the major benzoic acid derivatives from vegetables and fruits with a strong antioxidative effect, 10-fold higher than that of α-tocopherol [23]. PA, even at 100 ppm in a diet, shows potent chemopreventive effects on colon and oral carcinogenesis in rats [24]. A recent study [25] was initially performed to estimate the effectiveness of PA against TPA-induced tumor promotion in mouse skin. Interestingly, the modulation of tumor development was apparently dependent on the dose (1.6∼20,000 nmol) and timing (5 min∼3 h before TPA treatment) of PA application. We have demonstrated not only the lack of an inhibitory effect but also significant enhancement of mouse skin tumor promotion by pretreatment with a high dose (> 1600 nmol) of PA at an appropriate interval (3 h before TPA application). The possibility that metabolism by tyrosinase activity of PA to certain compound(s) without antioxidative properties and/or with tumor promotional potency has also been speculated.
The present study was undertaken to address whether or not PA modifies TPA-induced chronic inflammation in mouse skin using the multiple-application model. To gain further evidence that the tyrosinase-derived reactive quinone intermediate(s) of PA is indeed involved in skin inflammatory responses such as recruitment of leukocytes generating tumor-promoting oxygen radicals, we examined the enhancing effects of PA on TPA-induced inflammation in both a TPA-resistant and tyrosinase-dominant mouse strain. In addition, contact hypersensitivity by PA was documented for the first time.
Section snippets
Chemicals and animals
PA was purchased from Nacalai Tesque, Inc., Kyoto, Japan. TPA was obtained from Research Biochemicals International, Natick, MA, USA. RPMI 1640 medium was purchased from Gibco RBL, Rockville, MD, USA. All other chemicals were purchased from Wako Pure Chemical Industries, Osaka, Japan. Female ICR mice (7 weeks old) were obtained from Japan SLC, Shizuoka, Japan. Female B6C3F1 mice (7 weeks old) were obtained from Charles River Japan Inc., Yokohama City, Japan. Mice used in each experiment were
Tyrosinase activity in the ICR and B6C3F1 mouse
The dopa oxidation activity of tyrosinase in the skin from albino ICR and black B6C3F1 mice was assayed using a typical colorimetric method [26]. A weak but significant tyrosinase activity in albino ICR mouse skin was detected. In the extract from B6C3F1 mouse skin, dopa quinone was produced in more than 10 times the amount as that from ICR mouse skin (Fig. 2). TPA application to these mouse skins did not affect the tyrosinase activity (data not shown).
The modifying effect of PA on acute inflammation in B6C3F1 mouse skin
Because the enhancing effects of high
Discussion
PA is well known to be one of the major strong antioxidants from vegetables and fruit, and a promising cancer chemopreventor, as mentioned above. The recent study, however, demonstrated the significant enhancement of mouse skin tumor promotion by pretreatment with a high dose of PA at an appropriate interval, and the possibility of metabolism of PA to certain compound(s) without antioxidative properties and/or with tumor promotional potency [25]. The present study utilizing acute and chronic
Acknowledgements
This study was supported by grants-in-aid for Scientific Research on Priority Areas—Cancer—(H.O.) and JSPS Research Fellow (Y.N.) from the Ministry of Education, Science, Sports, and Culture of Japan, and by a subsidy from the Asahi Beer Foundation for the Promotion of Science.
References (51)
- et al.
Spin trapping evidence for myeloperoxidase-dependent hydroxyl radical formation by human neutrophils and monocytes
J. Biol. Chem.
(1992) - et al.
A diacetylenic spiroketal enol ether epoxide, AL-1, from Artemisia lactiflora inhibits 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion possibly by suppression of oxidative stress
Cancer Lett.
(1999) - et al.
Role of inflammatory cells in the metabolic activation of polycyclic aromatic hydrocarbons in mouse skin
Toxicol. Appl. Pharmacol.
(1987) - et al.
A comparison of scavenging abilities of antioxidants against hydroxyl radicals
Arch. Biochem. Biophys.
(1996) - et al.
Inhibitory effects of pheophorbide a, a chlorophyll-related compound, on skin tumour promotion in ICR mouse skin
Cancer Lett.
(1996) - et al.
Modulation of fatty acid oxidation alters contact hypersensitivity to urushiolsrole of aliphatic chain beta-oxidation in processing and activation of urushiols
J. Invest. Dermatol.
(1997) - et al.
Melanogenesis-targeted anti-melanoma pro-drug developmenteffect of side-chain variations on the cytotoxicity of tyrosinase-generated ortho-quinones in a model screening system
Eur. J. Cancer
(1997) - et al.
Antioxidants-carcinogenic and chemopreventive properties
Adv. Cancer Res.
(1989) - et al.
Inflammation and oxidative stress in carcinogenesis
Cancer Cells
(1991) - et al.
Leukocyte oxygen activation and microbicidal oxidative toxin
Crit. Rev. Biochem. Mol. Biol.
(1989)
Intracellular singlet oxygen generation by phagocytosing neutrophils in response to particles coated with a chemical trap
J. Biol. Chem.
Suppression of tumor promoter-induced oxidative stress and inflammatory responses in mouse skin by a superoxide generation inhibitor 1′-acetoxychavicol acetate
Cancer Res.
Oxygen radical-dependent epoxydation of (7S,8S)-dihydroxy-7,8-dihydrobenzo[a]pyrene in mouse skin in vivo. Stimulation by phorbol esters and inhibition by antiinflammatory steroids
J. Biol. Chem.
In vivo formation of oxidized DNA bases in tumor promoter-treated mouse skin
Cancer Res.
Suppression of tumor promoter-induced oxidative events and DNA damage in vivo by sarcophytol Aa possible mechanism of antipromotion
Cancer Res.
Relationship of oxidative events and DNA oxidation in SENCAR mice to in vivo promoting activity of phorbol ester-type tumor promoters
Carcinogenesis
Inhibitory effects of curcumin and tetrahydrocurcuminoids on the tumor promoter-induced reactive oxygen species generation in leukocytes in vitro and in vivo
Jpn. J. Cancer Res.
Kurosu, a traditional vinegar produced from unpolished rice, suppresses lipid peroxidation in vitro and in mouse skin
Biosci. Biotechnol. Biochem.
Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice
Cancer Res.
Suppression by sitrus auraptene of phorbol ester- and endotoxin-induced inflammatory responsesrole of attenuation of leukocyte activation
Carcinogenesis
Search for naturally-occurring antioxidative chemopreventors on the basis of the involvement of leukocyte-derived reactive oxygen species in carcinogenesis
Asian Pac. J. Cancer Prev.
Chemopreventive effect of a xanthine oxidase inhihitor, 1′-acetoxychavicol acetate, on rat oral carcinogenesis
Jpn. J. Cancer Res.
A xanthine oxidase inhihitor 1′-acetoxychavicol acetate inhibits azoxymethane-induced colonic aberrant crypt foci in rats
Carcinogenesis
Chemoprevention of azoxymethane-induced rat colon carcinogenesis by a xanthine oxidase inhibitor, 1′-acetoxychavicol acetate
Jpn. J. Cancer Res.
Citrus auraptene inhibits chemically induced colonic aberrant crypt foci in male F344 rats
Carcinogenesis
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Present address: Laboratory of Food and Biodynamics, Nagoya University Graduate School of Bioagricultural Sciences, Nagoya 464-8601, Japan.