Inhibition of 12-<i>O</i>-tetradecanoylphorbol-13-acetate-mediated epidermal ornithine decarboxylase induction and skin tumor promotion by new lipoxygenase inhibitors lacking protein kinase C inhibitory effects

Aizu, Eriko; Nakadate, Teruo; Yamamoto, Shozo; Kato, Ryuichi

doi:10.1093/carcin/7.11.1809

Cited by 36 publications

(14 citation statements)

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“…Reports have indicated that butein can suppress the proliferation of breast carcinoma, colon carcinoma, osteosarcoma, lymphoma, acute myelogenous leukemia, chronic myeloid leukemia, multiple myeloma, melanoma, and hepatic stellate cells [198][199][200]. Moreover, it was found to suppress phorbol ester-induced skin tumor formation [201,202], reduce antibodyassociated glomerulonephritis [203], and suppress liver fibrosis induced by carbon tetrachloride [204]. Furthermore, butein was also found to induce G 2 /M phase arrest and apoptosis in hepatocellular carcinoma (HCC) cells through reactive oxygen species (ROS) generation [205], suggesting that butein may have a great potential for HCC treatment.…”

Section: Buteinmentioning

confidence: 99%

Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors

Siveen

Sikka

Surana

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

481

510

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Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic transcription factors that mediate intracellular signaling that is usually generated at cell surface receptors and thereby transmit it to the nucleus. Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human tumors, including hematological malignancies (leukemias, lymphomas, and multiple myeloma) as well as diverse solid tumors (such as head and neck, breast, lung, gastric, hepatocellular, colorectal and prostate cancers). There is strong evidence to suggest that aberrant STAT3 signaling promotes initiation and progression of human cancers by either inhibiting apoptosis or inducing cell proliferation, angiogenesis, invasion, and metastasis. Suppression of STAT3 activation results in the induction of apoptosis in tumor cells, and accordingly its pharmacological modulation by tyrosine kinase inhibitors, antisense oligonucleotides, decoy nucleotides, dominant negative proteins, RNA interference and chemopreventive agents have been employed to suppress the proliferation of various human cancer cells in culture and tumorigenicity in vivo. However, the identification and development of novel drugs that can target deregulated STAT3 activation effectively remains an important scientific and clinical challenge. This review presents the evidence for critical roles of STAT3 in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT3 signaling cascade.

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Section: Buteinmentioning

confidence: 99%

Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors

Siveen

Sikka

Surana

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

481

510

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“…AA-861 Blocks the Generation of 12/15-LOX-derived Metabolites during Implantation-To address 12/15-LOX function in the pregnant uterus, we used AA-861, a coenzyme Q-like compound that is reported to inhibit LOX activity in certain tissues without affecting the other arachidonic acid-metabolizing enzymes COX-1 and COX-2 that produce various prostaglandins (21)(22)(23). To test the specificity of this inhibitor, we initially examined its effects on both COX and 12/15-LOX activities in the uterus at the time of implantation.…”

Section: Induction Of L-and E-12/15-lox Gene Expression In the Pregnamentioning

confidence: 99%

A Novel Pathway Involving Progesterone Receptor, 12/15-Lipoxygenase-derived Eicosanoids, and Peroxisome Proliferator-activated Receptor γ Regulates Implantation in Mice

Cheon

Kannan

et al. 2004

Journal of Biological Chemistry

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The 12/15-lipoxygenases (12/15-LOX) catalyze the stereo-specific oxygenation of arachidonic and linoleic acids into a complex series of signaling molecules, including the hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs). Our previous studies, using high density oligonucleotide microarrays, suggested a novel link between progesterone receptor (PR) signaling and 12/15-LOX-mediated fatty acid metabolism in preimplantation mouse uterus. In this paper, using PR knockout mice, we established that The steroid hormones progesterone (P) 1 and estrogen (E) play crucial roles during early pregnancy by coordinating a complex series of interactions between the implanting blastocyst and the uterus (1-5). In mice, implantation is initiated 4 days after fertilization when the blastocyst reaches the uterus (1, 6). It is thought that the action of the steroid hormones during the preimplantation phase prepares the endometrium for the attachment of the blastocyst and the subsequent events leading to the establishment of pregnancy. The cellular effects of P and E are mediated through intracellular progesterone receptor (PR) and estrogen receptor, which are hormone-inducible transcription factors (7,8). Hormone-occupied PR or estrogen receptor triggers the expression of specific gene networks in different cell types within the uterus, and the products of these genes mediate the hormonal effects during implantation. In order to understand the molecular basis of this complex physiological process, it is critical to identify the steroid-regulated pathways that are induced or suppressed at the time of implantation and analyze their functional roles.We recently used RU486, a well characterized antiprogestin, as a tool to uncover the PR signaling pathways in the pregnant uterus (9). RU486 counteracts the action of P by binding directly to PR and impairing its gene regulatory function (10, 11). Administration of RU486 to pregnant rodents during the preimplantation phase effectively blocks implantation by inhibiting PR-dependent gene expression (12). By using oligonucleotide microarrays, we identified several potential PR-regulated genes whose expression was markedly altered by RU486 in the uterus at the time of implantation (9). Interestingly, two of the mRNAs repressed in response to RU486 were leukocyte-12/15-lipoxygenase (L-12/15-LOX) and epidermal-12/15-lipoxygenase (E-12/15-LOX), which belong to a family of polyunsaturated fatty acid-metabolizing enzymes.The lipoxygenases metabolize arachidonic and linoleic acids, which are major cellular substrates in the synthesis of biological mediator substances known as eicosanoids (13, 14). There are three major types of mammalian lipoxygenase activity: 5-LOX, 12-LOX, and 15-LOX. The primary metabolites of arachidonic acid generated by the 5-LOX are the leukotrienes and lipoxines, whereas the 12-and 15-LOX enzymes produce hydroxyeicosatetraenoic acids (HETEs) (15,16). Metabolism of

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“…In vivo, AA-861 (15 µM/mouse) strongly suppressed DMBA and TPA-induced skin tumours and at 1 -30 µM dose-dependently inhibited TPA-stimulated ornithine decarboxylase (ODC) activity in mouse skin [133]. In vitro, AA-861 exerted antiproliferative activity in three human leukaemia (K562, Molt4B and HL60) and one cervical cell line (HeLa) [134].…”

Section: -Lo Inhibitorsmentioning

confidence: 99%

Potential use of lipoxygenase inhibitors for cancer chemoprevention

Steele¹,

Holmes²,

Hawk³

et al. 2000

Expert Opinion on Investigational Drugs

161

170

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Increasing evidence suggests that lipoxygenase (LO)-catalysed metabolites have a profound influence on the development and progression of human cancers. Compared with normal tissues, significantly elevated levels of LO products have been found in breast tumours, colon cancers, lung, skin and prostate cancers, as well as in cells from patients with both acute and chronic leukaemias. LO-mediated products elicit diverse biological activities needed for neoplastic cell growth, influencing growth factor and transcription factor activation, oncogene induction, stimulation of tumour cell adhesion and regulation of apoptotic cell death. Agents that block LO catalytic activity may be effective in preventing cancer by interfering with signalling events needed for tumour growth. In the past ten years, pharmaceuticals agents that specifically inhibit the 5-LO metabolic pathway have been developed to treat inflammatory diseases such as asthma, arthritis and psoriasis. Some of these compounds possess anti-oxidant properties and may be effective in preventing cancer by blocking free radical-induced genetic damage or by preventing the metabolic activation of carcinogens. Other compounds may work by negatively modulating DNA synthesis. Pharmacological profiles of potential chemopreventive agents are compiled from enzyme assays, in vitro testing (e.g., cell proliferation inhibition in human cancer cells) and in vivo animal carcinogenesis models (e.g., N-methyl-N-nitrosourea-induced rat mammary cancer, benzo(a)pyrene-induced lung tumours in strain A/J mice and hormone-induced prostate tumours in rats). In this way, compounds are identified for chemoprevention trials in human subjects. Based on currently available data, it is expected that the prevention of lung and prostate cancer will be initially studied in human trials of LO inhibitors.

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Inhibition of 12-O-tetradecanoylphorbol-13-acetate-mediated epidermal ornithine decarboxylase induction and skin tumor promotion by new lipoxygenase inhibitors lacking protein kinase C inhibitory effects

Cited by 36 publications

References 0 publications

Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors

Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors

A Novel Pathway Involving Progesterone Receptor, 12/15-Lipoxygenase-derived Eicosanoids, and Peroxisome Proliferator-activated Receptor γ Regulates Implantation in Mice

Potential use of lipoxygenase inhibitors for cancer chemoprevention

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