• Title, Summary, Keyword: tumor promotion

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Paris polyphylla Smith Extract Induces Apoptosis and Activates Cancer Suppressor Gene Connexin26 Expression

  • Li, Fu-Rong;Jiao, Peng;Yao, Shu-Tong;Sang, Hui;Qin, Shu-Cun;Zhang, Wei;Zhang, Ya-Bin;Gao, Lin-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.205-209
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    • 2012
  • Background: The inhibition of tumor cell growth without toxicity to normal cells is an important target in cancer therapy. One possible way to increase the efficacy of anticancer drugs and to decrease toxicity or side effects is to develop traditional natural products, especially from medicinal plants. Paris polyphylla Smith has shown anti-tumour effects by inhibition of tumor promotion and inducement of tumor cell apoptosis, but mechanisms are still not well understood. The present study was to explore the effect of Paris polyphylla Smith extract (PPSE) on connexin26 and growth control in human esophageal cancer ECA109 cells. Methods: The effects of PPSE on Connexin26 were examined by RT-PCR, western blot and immunofluorescence; cell growth and proliferation were examined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Results: PPSE inhibited the growth and proliferation on esophageal cancer ECA109 cells, while increasing the expression of connexin26 mRNA and protein; conversely, PPSE decreased Bcl-2 and increased Bad. Conclusion: This study firstly shows that PPSE can increase connexin26 expression at mRNA and protein level, exerting anti-tumour effects on esophageal cacner ECA109 cells via inhibiting cell proliferation and inducing cell apoptosis.

Analysis of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin Induced Gene Expression Profile in Hairless Mice Skin Using Pathway Specific cDNA Microarray

  • Ryeom, Tai-Kyung;Kang, Ho-Il;Kang, Mi-Kyung;Eom, Mi-Ok;Park, Mi-Sun;Jee, Seung-Wan;Kim, Ok-Hee
    • Proceedings of the Korean Society of Toxicology Conference
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    • pp.179-179
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    • 2003
  • 2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin (TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanisms of TCDD-induced carcinogenesis are poorly understood, it considered to be non-genotoxic and tumor promoter. In this study, we investigated the tumor promotion effect of TCDD on the two-stage skin chemical carcinogenesis using hairless mouse (SKH1).(omitted)

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Anti-tumor Promoting Activity of Some Malaysian Traditional Vegetables (Ulam)

  • Mooi, L. Yang;Ali, A.M.;Norhanom, A.B.;Salleh, K. Mat;Murakami, A.;Koshimizu, K.
    • Natural Product Sciences
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    • v.5 no.1
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    • pp.33-38
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    • 1999
  • Ethanolic extracts of different parts of 10 local traditional vegetables (ulam) (Amaranthus gangeticus, Jussiaea linifolia, Eugenia polyantha, Trapa incisa, Trichosanthes anquina, Mangifera indica, Pachyrrhirus erosus, Barringtonia mcarostachya, Carica papaya, and Coleus tuberosus) were screened for in vitro antitumor promoting activity using the inhibition test of Epstein-Barr virus (EBV) activation in Raji cells induced by phorbol 12-myristate 13-acetate and sodium-n-butyrate. All the extracts were found to have strong inhibition activity toward EBV-activation, except for leaf extract of T. anquina. The extracts were non-cytotoxic to the Raji cells except for the extracts of A. gangeticus (leaves), B. macrostachya (leaves), E. polyantha (young leaves), and J. linifolia (leaves) where the viability of the cells were decreased significantly.

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SUPPRESSION OF PHORBOL ESTER-INDUCED EXPRESSION OF CYCLLOOXYGENASE-2 AND INDUCIBLE NITRIC OXIDE SYNTHASE BY SELCTED CHEMOPREVENTIVE PHYTOCHEMICALS VIA DOWN-REGULATION OF NF-$\textsc{k}$B

  • Surh, Young-Joon
    • Proceedings of the Korean Society of Toxicology Conference
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    • pp.88.2-98
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    • 2002
  • A wide arry of naturally occurring substances particularly those present in dietary and medicinal plants, have been reported to possess substantial cancer chemopreventive properties. Certain phytochemicals retain strong antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activities. Inducible cyclooxygenase(COX-2) and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. There is some evidence that expression of both COX-2 and iNOS is co-regulated by the eukaryotic transcription factor NF-$textsc{k}$B. Increased expression of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory diseases. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activies are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. An example is curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), that strongly occurring diaryl heptanoids structurally related to curcumin have substantial anti-tumor promotional activities in two-stage mouse skin carcinogenesis. Thus, yakuchinone A [1-(4'-hydroxy-3'-methoxyphenyl)-7-phenyl-3heptanone] and yakuchinone B [1-(4'-hydroxy-3'methoxyphenyl)-7-phenylhept-1-en-3-one] present in Alpinia oxyphylla Miquel (Zingiberacease) attenuate phorbol ester-induced inflammation and papilloma formation in female ICR mice. These diarylheptanoids also suppressed phorbol ester-induced activation of epdermal ornithine decarboxylase and its mRNA expression when applied onto shaven backs of mice. Yakuchinone A and B as well as curcumin inhibited phorbol ester-induced expression of COX-2 and iNOS and their mRNA in mouse skin via inactivation of NF-$textsc{k}$B. Capsaicin, a major pungent ingredient of red pepper also attenuated phorbol ester-induced NF-$textsc{k}$B activation. Similar suppression of COX-2 and iNOS and down-regulation of NF-$textsc{k}$B activation for its DNA binding were observed with the ginsenosied Rg3 and the ethanol extract of Artemisia asiatica. We have also found that certain anti-inflammatory phytochemicals exert inhibitory effects on phorbol ester-induced COX-2 expression and NF-$textsc{k}$B activation in immortalized human breast epithelial (MCF-10A) cells in culture. One of the plausible mechanisms undelying inhibition by aforementioned phytochemicals of phorbol ester-induced NF-$textsc{k}$B activation involves interference with degragation of the inhibitory unit, I$textsc{k}$Ba, which blocks subsequent nuclear translocation of the functionally active p65 subunit of NF-$textsc{k}$B. the activation of epidermal NF-$textsc{k}$B by phorbol ester and subsequent induction of COX-2 hence appear to play an important role in intracellular signaling pathwasy leading to tumor promotion and targeted inhibition of NF-$textsc{k}$B may provide a new promising cancer chemopreventive strategy.

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A Study on Abdomen Ultrasonography Classified by Particular Disease Practiced in Health Promotion Center of a University Hospital (한 대학병원 종합건강진단센터에서 시행한 복부 초음파검사의 유소견 연구)

  • Kim, Nam-Hee;Choi, Jong-Hak
    • Journal of radiological science and technology
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    • v.24 no.1
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    • pp.33-41
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    • 2001
  • This study is to get preliminary data for an effectiveness evaluation of abdominal examination and improvement of it. Abnormal cases of abdominal ultrasonography are classified by sex, frequency, diagnosis and age. 4,924 examinees were included at a university hospital of health promotion center from January to December in 1999. The results are as follows. 1. According to the distribution of sex, there are more male patients(55.0%) than females patients(48.0%). For men, 40's showed the highest percentage among examinees. For women, 50's were the highest. 2. The reason that they visited the health promotion center was that 'they wanted to check their health status'. This answers were reported the highest(59.3%). 3. Patients that had abnormal cases of abdominal ultrasonography were 48.3%. Liver, kidney, gallbladder showed the highest percentage of abnormal cases in order of organs. Additionally, abnormal cases were discovered in liver cases. 4. According to the frequency of abnormal cases among examinees, the slight fatty liver were the highest regardless of sex. Men had the slight fatty liver, kidney simple cyst, liver calcification and liver simple cyst in order of abnormal cases. Women showed the slight fatty liver kidney simple cyst, kidney calcification, liver simple cyst, and blood vessel tumor in order of abnormal cases. 5. For the abnormal cases of liver by sex and age, the 50's reported the highest number of abnormal cases in men(299 patients). In addition, 60's had the highest of disease rata 47.8%. For women, 50's reported the highest number of abnormal cases(361 patients). Over 70's patients had the highest of disease rata 52.6%. For kidney, men and women showed the highest number of abnormal cases -62 vs 44 respectively. Over 70's patients had the highest percentage of disease rata-23.2% vs 14.0% respectively. For gallbladder, the number of abnormal cases were the most in men's 60's (31 patients) and in women's in the same age group (32patients). Disease showed the highest percentage in men's 60's(7.6%) and in women's 70's (14.0%). 6. According to malignant tumor, 17patients were liver cancer, 2patients stomach ca and 1pt kidney cancer. 7. The relationship between the malignant tumor and the examination motive was that 'they wanted to check their health status(41.0%)' and 'regular checkup (24.0%)'.

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Role of NF-kB in the promotion of hepatocarcinogenesis by chemicals

  • Howard P. Glauert;Mason, Karen-Calfee;Yixin Li;Zijing Lu;Vani Nilakantan;Job Tharappel;Larry W. Robertson;Brett T. Spear
    • Proceedings of the Korean Society of Toxicology Conference
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    • pp.94-95
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    • 2001
  • The purpose of these studies was to determine if hepatic tumor promoters could activate the transcription factor NF-kB, the mechanism of this activation, and whether activation of NF-kB is important in the carcinogenic process. We first demonstrated that the administration of the peroxisome proliferator ciprofibrate increases the hepatic DNA binding activity of NF-kB in rats and mice.(omitted)

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Osteopontin and Developing Kidney (Osteopontin과 신장 발달)

  • Yim Hyung-Eun;Yoo Kee-Hwan
    • Childhood Kidney Diseases
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    • v.10 no.1
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    • pp.1-7
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    • 2006
  • Osteopontin (OPN) is a glycosylated phosphoprotein which mediates cell adhesion and migration, and is produced by bone, macrophages, endothelial cells, and epithelial cells. The many regulatory functions of OPN include bone remodeling, tumor invasion, wound repair, and promotion of cell survival. It is produced by renal tubular epithelial cells, and expression is upregulated in glomerulonephritis, hypertension, ischemic acute renal failure, renal ablation, and UUO. In this review, we discuss about osteopontin in general aspect, expression, role on the development and pathologic condition of neonatal kidney.

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The Role of Stem Cells and Gap Junctional Intercellular Communication in Carcinogenesis

  • Trosko, James E.
    • BMB Reports
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    • v.36 no.1
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    • pp.43-48
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    • 2003
  • Understanding the process of carcinogenesis will involve both the accumulation of many scientific facts derived from molecular, biochemical, cellular, physiological, whole animal experiments and epidemiological studies, as well as from conceptual understanding as to how to order and integrate those facts. From decades of cancer research, a number of the "hallmarks of cancer" have been identified, as well as their attendant concepts, including oncogenes, tumor suppressor genes, cell cycle biochemistry, hypotheses of metastasis, angiogenesis, etc. While all these "hallmarks" are well known, two important concepts, with their associated scientific observations, have been generally ignored by many in the cancer research field. The objective of the short review is to highlight the concept of the role of human adult pluri-potent stem cells as "target cells" for the carcinogenic process and the concept of the role of gap junctional intercellular communication in the multi-stage, multi-mechanism process of carcinogenesis. With these two concepts, an attempt has been made to integrate the other well-known concepts, such as the multi-stage, multi-mechanisn or the "initiation/promotion/progression" hypothesis; the stem cell theory of carcinogenesis; the oncogene/tumor suppression theory and the mutation/epigenetic theories of carcinogenesis. This new "integrative" theory tries to explain the well-known "hallmarks" of cancers, including the observation that cancer cells lack either heterologous or homologous gap junctional intercellular communication whereas normal human adult stem cells do not have expressed or functional gap junctional intercellular communication. On the other hand, their normal differentiated, non-stem cell derivatives do express connexins and express gap junctional intercellular communication during their differentiation. Examination of the roles of chemical tumor promoters, oncogenes, connexin knock-out mice and roles of genetically-engineered tumor and normal cells with connexin and anti-sense connexin genes, respectively, seems to provide evidence which is consistent with the roles of both stem cells and gap junctional communication playing a major role in carcinogenesis. The integrative hypothesis provides new strategies for chemoprevention and chemotherapy which focuses on modulating connexin gene expression or gap junctional intercellular communication in the premalignant and malignant cells, respectively.

Cancer Chemopreventive Properties of Processed Ginseng

  • Surh, Young-Joon
    • Proceedings of the Ginseng society Conference
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    • pp.270-280
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    • 1998
  • Ginseng is one of the most widely used medicinal plants, particularly in East Asian countries. Certain fractions or purified ingredients of ginseng have been shown to exert inhibitory effects on growth of cancer cells in culture or on tumorigenesis in experimental animals. Moreover, a recent epidemiologic study reveals that ginseng intake is associated with a reduced risk for environmentally related cancers such as esophageal, gastric, colorectal, and pulmonary tumors. Heat treatment of Panax ginseng C. A. Meyer at the temperature higher than that applied to the conventional preparation of red ginseng yielded a mixture of saponins with potent antioxidative properties. Thus, the methanol extract of heat-processed ginseng (designated as'NGMe') attenuated lipid peroxidation in rat brain homogenates induced by ferric ion or ferric ion plus ascorbic acid. Furthermore, the extract protected against strand scission in f Xl 74 supercoiled DNA Induced by UV photolysis of H2O2 and was also capable of scavenging superoxide generated in vitro by xanthine/xanthine oxidate or in differentiated human promyelocytic leukemia (HL-60) cells by the tumor promoter,12-0-tetvade- canoylphorbol-13-acetate (TPA). Since tumor promotion is closely linked to oxidative stress, we have determined possible anti-tumor promotional effects of NGMe on two-stage mouse skin tumorigenesis. Topical application of NGMe onto shaven backs of female ICR mice 10 min prior to TPA significantly ameliorated skin papillomagenesi s initiated by 7,12-dimethylbenz (a) anthracene (DMBA).'Likewise, TPA-induced epidermal ornithine decarboxylase activity and elevation of tumor necrosis factor-a were suppressed signifies%fly by NGMe pretreatment. NGMe topically applied onto surface of hamster buccal pouch 10 min before each topical application of DMBA inhibited oral carcinogenesis by 76olo in terms of multiplicity. Taken together, these results suggest that processed Panax ginseng C. A. Meyer has potential cancer chemopreventive activities.

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Finasteride Increases the Expression of Hemoxygenase-1 (HO-1) and NF-E2-Related Factor-2 (Nrf2) Proteins in PC-3 Cells: Implication of Finasteride-Mediated High-Grade Prostate Tumor Occurrence

  • Yun, Do-Kyung;Lee, June;Keum, Young-Sam
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.49-53
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    • 2013
  • A number of naturally-occurring or synthetic chemicals have been reported to exhibit prostate chemopreventive effects. Synthetic $5{\alpha}$-reductase (5-AR) inhibitors, e.g. finasteride and durasteride, gained special interests as possible prostate chemopreventive agents. Indeed, two large-scale epidemiological studies have demonstrated that finasteride or durasteride significantly reduced the incidence of prostate cancer formation in men. However, these studies have raised an unexpected concern; finasteride and durasteride increased the occurrence of aggressive prostate tumor formation. In the present study, we have observed that treatment of finasteride did not affect the growth of androgen-refractory PC-3 prostate cancer cells. Finasteride also failed to induce apoptosis or affect the expression of proto-oncogenes in PC-3 cells. Interestingly, we found that treatment of finasteride induced the expression of Nrf2 and HO-1 proteins in PC-3 cells. In particular, basal level of Nrf2 protein was higher in androgen-refractory prostate cancer cells, e.g. DU-145 and PC-3 cells, compared with androgen-responsive prostate cancer cells, e.g. LNCaP cells. Also, treatment of finasteride resulted in a selective induction of Nrf2 protein in DU-145 and PC-3 cells, but not in LNCaP cells. In view of the fact that upregulation of Nrf2-mediated phase II cytoprotective enzymes contribute to attenuating tumor promotion in normal cells, but, on the other hand, confers a selective advantage for cancer cells to proliferate and survive against chemical carcinogenesis and other forms of toxicity, we propose that finasteride-mediated induction of Nrf2 protein might be responsible, at least in part, for an increased risk of high-grade prostate tumor formation in men.