• Title/Summary/Keyword: Cancer chemoprevention

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Immunomodulatory Effects of Hexane Insoluble Fraction of Ficus septica Burm. F. in Doxorubicin-treated Rats

  • Nugroho, Agung Endro;Hermawan, Adam;Nastiti, Kunti;Suven, Suven;Elisa, Pritha;Hadibarata, Tony;Meiyanto, Edy
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5785-5790
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    • 2012
  • The use of chemotherapeutics induces cardiotoxicity and affects immune functions, therefore development of combinatorial agents against cardiotoxicity and immunosuppression needs to be explored. Previous studies of the hexane insoluble fraction (HIF) of an ethanolic extract of Ficus septica leaves showed anticancer effects singly and in combination with doxorubicin on T47D breast cancer cells. In this present study, it was evaluated for its immunomodulatory activities in doxorubicin-treated rats. Thirty male Sprague Dawley rats were divided into five groups consisting of six rats each as follows: Group 1, receiving oral saline 10 ml/kg BW (control group); Group 2, receiving HIF dose 750 mg/kg BW orally, once daily; Group 3, receiving HIF dose 1.500 mg/kg BW orally, once daily; Group 4, given oral saline 10 ml/kg BW (normal group); Group 5, receiving HIF dose 1.500 mg/kg BW orally, once daily. The rats of group 1-3 were intramuscularly administered with doxorubicin at a dose of 4.67 mg/kg BW at the days 1 and 4 to suppress immune functions. Concomitantly, the rats were treated with saline or HIF for seven consecutive days (1 to 7). Treatment of HIF succeeded in reducing side effects of doxorubicin based on increasing lymphocyte density and phagocytosis activity and capacity of macrophages, as well as increasing the CD8+ blood level and decreasing spleen IL-10 expression. Hexane insoluble fraction of of ethanolic extract of Ficus septica leaves has potential as a protective agent combined with doxorubicin.

Free Radical Toxicology and Cancer Chemoprevention

  • Lin, Jen-Kun
    • Toxicological Research
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    • v.17
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    • pp.83-88
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    • 2001
  • Most reactive oxygen species (ROS) are free radicals and implicated in the development of a number of disease processes including artherosclerosis, neurodegenerative disorders, aging and cancer. ROS are byproducts of a number of in vivo metabolic processes and are formed deliberately as part of nor-mal inflammatory response. On the other hand, ROS are generated either as by products of oxygen reduction during xenobiotic metabolism or are liberated as the result of the futile redox cycling of the chemical agents including several chemical carcinogens. A better understanding of the mechanisms of free radical toxicity may yield valuable clue to risks associated with chemical exposures that leading to the development of chronic diseases including cancer. The molecular biology of ROS-mediated alterations in gene expression, signal transduction and carcinognesis is one of the important subjects in free radical toxicology. Epidemiological studies suggest that high intake of vegetables and fruits are associated with the low incidence of human cancer. Many phytopolyphenols such as tea polyphenols, curcumin, resveratrol, apigenin, genistein and other flavonoids have been shown to be cancer chemopreventive agents. Most of these compounds are strong antioxidant and ROS scavengers in vitro and effective inducers of antioxidant enzymes such as superoxide dismutatse, catalase and glutathione peroxidase in vivo. Several cellular transducers namely receptor tyrosine kinase, protein kinase C, MAPK, PI3K, c-jun, c-fos, c-myc, NFkB, IkB kinase, iNOS, COX-2, Bcl-2, Bax, etc have been shown to be actively modulated by phyto-polyphenols. Recent development in free radical toxicology have provided strong basis for understanding the action mechanisms of cancer chemoprevention.

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Chemoprevention of Colon Cancer

  • Wakabayashi, Keiji
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.91-91
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    • 2003
  • Colon cancer is one of the most common malignancies in humans, and the search for effective chemopreventive agents is an important and urgent task. Expression levels of inflammation-related enzymes, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) are elevated in colon cancers, and their products, prostaglandins and nitric oxide, are suggested to be involved in colon carcinogenesis.(omitted)

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The Effects on Quinone ReductaseInduction of Daucus carota L. (당근 추출 성분의 Quinone reductase 유도활성 효과)

  • 한은주;노승배;배송자
    • Journal of Life Science
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    • v.10 no.1
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    • pp.79-85
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    • 2000
  • Chemoprevention is one of the major strategies for cancer control. It is well established that dietary factors play an important role in modulating the development of certain types of human cancer. The experiment was conducted to determine quinone reductase(QR) activity induction of Daucus carota L. on HepG2 cells. Among various partition layers of roots of Daucus carota L., the ethyl acetate partition layer(DCMEA) and the n-hexane partition layer(DCMH) tested to be most effective which resulted 2.1 and 1.6 respectively compared to the control value of 1.0. In the case of seeds of Daucus carota L. n-butanol partition layer (DCMB) on HepG2 cells at a dose of 200 $\mu\textrm{g}$/$m\ell$ showed the highest induction activity of QR which was 3.0. These results suggest that potentially useful cancer chemoprevention chemicals could be isolated from DCMEA and DCMH of the roots and DCMB of the seeds of Daucus carota L.

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Cancer Chemoprevention by Tea Polyphenols Through Modulating Signal Transduction Pathways

  • Lin, Jen-Kun
    • Archives of Pharmacal Research
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    • v.25 no.5
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    • pp.561-571
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    • 2002
  • The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

American ginseng attenuates azoxymethane/dextran sodium sulfate-induced colon carcinogenesis in mice

  • Yu, Chunhao;Wen, Xiao-Dong;Zhang, Zhiyu;Zhang, Chun-Feng;Wu, Xiao-Hui;Martin, Adiba;Du, Wei;He, Tong-Chuan;Wang, Chong-Zhi;Yuan, Chun-Su
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.14-21
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    • 2015
  • Background: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. Methods: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. Results: AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. Conclusion: AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.