Inhibition of Teleocidin-Caused Epidermal Ornithine Decarboxylase Induction by Phospholipase A2-, Cyclooxygenase- and Lipoxygenase-lnhibitors

Nakadate, Teruo; Aizu, Eriko; Yamamoto, Shozo; Fujiki, Hirota; Sügimura, Takashi; Kato, Ryuichi

doi:10.1254/jjp.37.253

Cited by 24 publications

(12 citation statements)

References 23 publications

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“…50 Agents that block induction of ODC can prevent tumor formation; therefore, its inhibition was shown to be a promising tool for screening inhibitors of tumorigenesis. 52,53 In the present study, topical application of PFE prior to that of TPA resulted in a significant inhibition of TPA-mediated induction of epidermal ODC activity and ODC protein expression (Figs. 3 and 4).…”

Section: Discussionsupporting

confidence: 53%

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

Afaq

Saleem

Krueger

et al. 2004

Intl Journal of Cancer

418

305

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Chemoprevention has come of age as an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable of intervening at more than one critical pathway in the carcinogenesis process will have greater advantage over other single-target agents. Pomegranate fruit extract (PFE) derived from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. Pomegranate fruit was extracted with acetone and analyzed based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and found to contain anthocyanins, ellagitannins and hydrolyzable tannins. We evaluated whether PFE possesses antitumor-promoting effects. We first determined the effect of topical application of PFE to CD-1 mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced conventional markers and other novel markers of skin tumor promotion. We found that topical application of PFE (2 mg/mouse) 30 min prior to TPA (3.2 nmole/mouse) application on mouse skin afforded significant inhibition, in a time-dependent manner, against TPA-mediated increase in skin edema and hyperplasia, epidermal ornithine decarboxylase (ODC) activity and protein expression of ODC and cyclooxygenase-2. We also found that topical application of PFE resulted in inhibition of TPA-induced phosphorylation of ERK1/2, p38 and JNK1/2, as well as activation of NF-B and IKK␣ and phosphorylation and degradation of I B␣. We next assessed the effect of skin application of PFE on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated CD-1 mouse. The animals pretreated with PFE showed substantially reduced tumor incidence and lower tumor body burden when assessed as total number of tumors per group, percent of mice with tumors and number of tumors per animal as compared to animals that did not receive PFE. In TPA-treated group, 100% of the mice developed tumors at 16 weeks on test, whereas at this time in PFE-treated group, only 30% mice exhibited tumors. Skin application of PFE prior to TPA application also resulted in a significant delay in latency period from 9 to 14 weeks and afforded protection when tumor data were considered in terms of tumor incidence and tumor multiplicity. The results of our study provide clear evidence that PFE possesses antiskintumor-promoting effects in CD-1 mouse. Because PFE is capable of inhibiting conventional as well as novel biomarkers of TPAinduced tumor promotion, it may possess chemopreventive activity in a wide range of tumor models. Thus, an in-depth study to define active agent(s) in PFE capable of affording antitumorpromoting effect is warranted.

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Section: Discussionsupporting

confidence: 53%

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

Afaq

Saleem

Krueger

et al. 2004

Intl Journal of Cancer

418

305

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“…Elevated levels of ODC gene products are consistently detected in transformed cell lines, virtually all-animal tumors and in certain tissues predisposed to tumorigenesis (Auvinen, 1997). As tumor formation can be prevented by the agents that block the induction of ODC (Verma et al, 1979;Nakadate et al, 1985), ODC inhibition was shown to be a promising tool for screening inhibitors of tumorigenesis. In the present study, topical application of Lupeol prior to that of TPA resulted in a significant inhibition of TPAmediated induction of epidermal ODC activity ( Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Lupeol modulates NF-κB and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice

et al. 2004

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Chemoprevention has become an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable for inhibition of promotion stage of tumorigenesis with the ability to intervene at several critical pathways in the tumorigenesis process will have greater advantage over other single-target agents. Lupeol, a triterpene, is the principal constituent of common fruit plants such as olive, mango, fig and medicinal herbs that have been used to treat skin aliments. Lupeol has been reported to possess a wide range of medicinal properties that include strong antioxidant, antimutagenic, anti-inflammatory and antiarthritic effects. In the present study, we show that Lupeol possesses antitumor-promoting effects in a mouse skin tumorigenesis model. We first determined the effect of topical application of Lupeol to CD-1 mouse against 12-Otetradecanoyl-phorbol-13-acetate (TPA)-induced conventional markers and other novel markers of skin tumor promotion. We found that topical application of Lupeol (1-2 mg/mouse) 30 min prior to TPA (3.2 nmol/mouse) application onto the skin of CD-1 mice afforded significant inhibition, in a time-and dose-dependent manner, against TPA-mediated increase in (i) skin edema and hyperplasia, (ii) epidermal ornithine decarboxylase (ODC) activity, and (iii) protein expression of ODC, cyclo-oxygenase-2 and nitric oxide synthase. As of the role of nuclear factor kappa B (NF-jB) and phosphatidyl inositol 3-kinase (PI3K)/Akt signaling in tumor promotion, we next determined the effect of topical application of Lupeol to mouse skin against these signaling pathways. We found that Lupeol treatment to mouse skin resulted in the inhibition of TPA-induced (i) activation of PI3K, (ii) phosphorylation of Akt at Thr 308 , (iii) activation of NF-jB and IKKa, and (iv) degradation and phosphorylation of IjBa. The animals pretreated with Lupeol showed significantly reduced tumor incidence, lower tumor body burden and a significant delay in the latency period for tumor appearance. At the termination of the experiment at 28 weeks, 100% of the animals in TPA-treated group exhibited seven to eight tumors/mouse, whereas only 53% of the mice receiving Lupeol prior to TPA treatment exhibited one to three tumors/mouse. These results for the first time provide evidence that Lupeol possesses antiskin tumor-promoting effects in CD-1 mouse and inhibits conventional as well as novel biomarkers of tumor promotion. We suggest that Lupeol is an attractive antitumor-promoting agent that must be evaluated in tumor models other than skin carcinogenesis.

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“…Arachidonic acid metabolites like HETE have been identified as mediators of tumor growth and progression in various organs, such as skin or pancreas, and inhibitors of LOX prevent tumor development in these organs (Belman et al 1989;Ding et al 1999;Nakadate et al 1985). On the cellular level both down modulation of bcl 2 and activation of caspase 3 have been shown in vascular smooth muscle cells (Nishio and Watanabe 1997).…”

Section: Discussionmentioning

confidence: 99%

Naturally occurring lignans efficiently induce apoptosis in colorectal tumor cells

Hausott

Greger

Marian

2003

Journal of Cancer Research and Clinical Oncology

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Plant-derived lignans caused cell loss by apoptosis in colorectal adenoma and carcinoma cells. Nordihydroguaiaretic acid (NDGA), commonly used for the inhibition of lipoxygenase isoenzymes, showed the strongest growth inhibition with an IC50 of 1.9+/-0.5 microg followed by epiashantin (IC50=9.8+/-4.5 microM) and arctigenin (IC50=16.5+/-8.5 microM). The lignans caused a time- and dose-dependent loss of mitochondrial membrane potential (MMP), down regulation of the anti-apoptotic protein bcl(xl) and an increase of the apoptotic index. The time interval until loss of MMP and down modulation of bcl(xl) became evident correlated with the efficiency of growth inhibition by NDGA, epiashantin and yangambin. Bcl2 and caspase 3 were not involved. NDGA also induced a shift of the culture population to the G2/M phase of the cell cycle. With respect to these results, naturally occurring lignans could be useful in the therapy and chemoprevention of colorectal tumors.

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Inhibition of Teleocidin-Caused Epidermal Ornithine Decarboxylase Induction by Phospholipase A2-, Cyclooxygenase- and Lipoxygenase-lnhibitors

Cited by 24 publications

References 23 publications

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

Lupeol modulates NF-κB and PI3K/Akt pathways and inhibits skin cancer in CD-1 mice

Naturally occurring lignans efficiently induce apoptosis in colorectal tumor cells

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