• Title/Summary/Keyword: Chemopreventive agents

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Action mechanism of Antiestrogenicity of Ginkgo biloba extracts and its major components in human breast cancer cell

  • Kim, Yun-Hee;Ryu, Byung-Taek;Oh, Seung-Min;Chung, Kyu-Hyuck
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.109.2-110
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    • 2003
  • Estrogen is the most important endocrine hormone that has reproduction and physiological process in a number of tissues. However, an excess of estrogen can promotes the growth of hormone-dependent breast cancer. Thus the regulation of estrogen level is important a prevention of estrogen-related cancer. It has been reported that some of flavonoids could inhibit estrogen-dependent cancer. And these compounds are expected as chemopreventive agents on estrogen related disease. (omitted)

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Effect of Thesium Chinese Turczaninow Aqua-acupuncture Solution and Astragail Radix Aqua-acupuncture Solution on Promotion/ progression of Carcinogenesis (하고초와 황기 약침액이 발암 진행과정에 미치는 영향)

  • 손윤희;박신화;류준선;조경희;임종국;남경수
    • Journal of Life Science
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    • v.11 no.4
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    • pp.335-339
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    • 2001
  • Cancer chemoprevention refers to the use of natural or synthetic substances to prevent initiational and promotional events that occur during the process of carcinogenesis. Thesium Chinese Turczaninow aqua-acupuncture solution (TCTAS) and Astragli Radix aqua-acupuncture solution (ARAS) were tested as the cancer chemopreventive agents using biochemical markers of carcinogenesis. The effects on the inhibition of phorbol 12- myristate 13-acetate(TPA)-induced free radical formation in HL-60 cells and the inhibition of polyamine metabolism were measured. There is significant inhibition of TAP-induced free radical formation in human leukemic cells with cells with ARAS. Proliferation of Acanthamoeba castellanii was inhibited by TCTAS and ARAS. TCTAS and ARAS positive in these assays may inhibit the carcinogenesis process and is considered promising cancer-preventing agents.

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Treatment of Rhus vernifciflua STOKES decoction to colorectal cancer patient (stage IV):single case report (옻나무 전탕추출물을 활용한 대장암 4기 환자치험 1례)

  • Kim, Bo-Geun;Park, Sang-Chae
    • Journal of Korean Traditional Oncology
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    • v.15 no.1
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    • pp.111-117
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    • 2010
  • Background & Objectives: Colorectal Cancer is 10% of all cancer incidence and the motality from colorectal cancer is nearly 450,000 a year. Since chemopreventive agents from Herbal medicine is hot issue recently, to prove antitumor effecicacy of Rhus vernifciflua STOKES decoction (Chijong-dan), clinical study was carried out. Here we report one patient with colorectal cancer of stage IV. The patient had a colorectal cancer (Stage IV, T4N2M1), lymph node metastases and underwent chemotherapy. Methods: The patient visited Hana oriental medicine Clinic in 2009 and was treated using Chijong-dan for 1 year at Hana Oriental Clinic. Results: Chijongdan showed no side effect during its treatment and tumor size was retarded based on CT scanning. Overall, this case report suggests that Rhus vernifciflua STOKES decoction can be a potent cancer preventive agents for colorectal cancer but it is still required to verify the scientific and clinical evidences for Rhus vernifciflua STOKES decoction (Chijong-dan).

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Inhibitory effects of natural products on lipopolysaccharide-stimulated PGE2 and nitric oxide production in RAW 264.7 cells

  • Park, Hye-Jin;Min, Hye-Young;Park, Dong-Ki;Lee, Sang-Kook
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.268.2-269
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    • 2003
  • Prostaglandins (PGs) and NO (nitric oxide) are important elements to keep homeostasis and host defense system in human beings. When PGs and NO are overproduced by cyclooxygenase-2(COX-2) and inducible nitric oxide synthase (iNOS), respectively, they can cause chronic inflammation, tissue damage, and carcinogenesis. On this line, we are interested in finding agents that can inhibit the production of PGs and NO from natural products for devloping anti-inflammatory and cancer chemopreventive agents. (omitted)

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Signal Transduction Events Elicited by Natural Products: Role of MAPK and Caspase Pathways in Homeostatic Response and Induction of Apoptosis

  • Kong, Ah-Ng Tony;Yu, Rong;Chen, Chi;Mandlekar, Sandhya;Primiano, Thomas
    • Archives of Pharmacal Research
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    • v.23 no.1
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    • pp.1-16
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    • 2000
  • Many natural products elicit diverse pharmacological effects. Using two classes of potential chemopreventive compounds, the phenolic compounds and the isothiocyanates, we review the potential utility of two signaling events, the mitogen-activated protein kinases (MAPKs) and the ICE/Ced-3 proteases (caspases) stimulated by these agents in mammalian cell lines. Studies with phenolic antioxidants (BHA, tBHQ), and natural products (flavonoids; EGCG, ECG, and isothiocyanates; PEITC, sulforaphane), provided important insights into the signaling pathways induced by these compounds. At low concentrations, these chemicals may activate the MAPK (ERK2, JNK1, p38) leading to gene expression of survival genes (c-Fos, c-Jun) and defensive genes (Phase II detoxifying enzymes; GST, QR) resulting in survival and protective mechanisms (homeostasis response). Increasing the concentrations of these compounds will additionally activate the caspase pathway, leading to apoptosis (potential cytotoxicity). Further increment to suprapharmacological concentrations will lead to nonspecific necrotic cell death. The wider and narrow concentration ranges between the activation of MAPK/gene induction and caspases/cell death exhibited by phenolic compounds and isothiocyanates, respectively, in mammalian cells, may reflect their respective therapeutic windows in vivo. Consequently, the studies of signaling pathways elicited by natural products will advance our understanding of their efficacy and safety, of which many man become important therapeuitc drugs of the future.

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Effects of Natural Products on the Induction of NAD(P)H: Quinone Reductase in Hepa 1c1c7 Cells for the Development of Cancer Chemopreventive Agents

  • Kim, Young-Mi;Chang, Il-Moo;Mar, Woong-Chon
    • Natural Product Sciences
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    • v.3 no.2
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    • pp.81-88
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    • 1997
  • NAD(P)H:quinone reductase (QR) is one of the protective phase II enzymes against toxicity that accomplishes the capacity of detoxification by modulating the effects of mutagens and carcinogens. The detoxification mechanism is that quinone reductase promotes the 2-electron reduction of quinones to hydroquinones which are less reactive. This study is to search new inducers of quinone reductase from natural products, which can be used as cancer chemopreventive agents. Plant extracts were evaluated by using quinone reductase generating system With Hepa 1c1c7 murine hepatoma cell lines for enzyme inducing properties and crystal violet staining method for the measurement of cytotoxicity provoked. We have tested approximately 106 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of natural products. The ethyl acetate fractions of Vitex rotundifolia $(fruits,\;2FC:\;12.7\;{\mu}g/ml)$, Cnidium officinale $(aerial\;parts,\;2FC:\;10.5\;{\mu}g/ml)$, Chrysanthemum sinese $(flowers,\;2FC:\;17.4{\mu}g/ml)$ and the hexane fractions of Angelica gigas $(roots,\;2FC:\;13.2\;{\mu}g/ml)$, Smilax china $(roots,\;2FC:\;l1.9\;{\mu}g/ml)$, Sophora flavescens $(roots,\;2FC:\;16.3\;{\mu}g/ml)$ revealed the significant induction of quinone reductase in a murine hepatic Hepa 1c1c7 cell culture system.

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Antioxidative Properties of Brown Algae Polyphenolics and Their Perspectives as Chemopreventive Agents Against Vascular Risk Factors

  • Kang, Keejung;Park, Yongju;Hwang, Hye-Jeong;Kim, Seong-Ho;Lee, Jeong-Gu;Shin, Hyeon-Cheol
    • Archives of Pharmacal Research
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    • v.26 no.4
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    • pp.286-293
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    • 2003
  • Several polyphenolic compounds and complex mixtures were isolated from brown algae species. The 1,1-diphenyl-2-picryhydarzyl (DPPH) radical scavenging activity and ferric reducing antioxidant power (FRAP) of these compounds were evaluated to determine their physiological usefulness as antioxidants for vascular protection. The antioxidative protection of low-density lipoprotein (LDL) was also evaluated and compared with that of catechin, because the generation of oxidized LDL is one of the most active and specific risk factors contributing to atherogenesis. Oral administration to rats of a commercially available sample ($VNP^{TM}$) containing 30% of these polyphenolic compounds and 70% dietary fiber revealed that the serum reducing capacity measured in terms of FRAP value was significantly elevated 30 min after the treatment, but declined rather quickly thereafter, indicating the good oral absorption of the compounds and their fast binding to the lumenal surface of the blood vessels. An eight-week, human, clinical trial (n=31) of $VNP^{TM}$ showed significant improvement in erectile function measured by IIEF (international index of erectile function) score. These results collectively demonstrated the usefulness of these polyphenolic compounds as fundamental chemopreventive agents against vascular risk factors originating from oxidative stress.

Screening of Quinone Reductase Inducers from Agricultural Byproducts Using Mouse Hepatoma Cell Line (Mouse hepatoma 세포를 이용한 농산부산물로부터 quinone reductase활성물질의 탐색)

  • Kim, Jong-Sang;Nam, Young-Jung;Kim, Joo-Won
    • Korean Journal of Food Science and Technology
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    • v.27 no.6
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    • pp.972-977
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    • 1995
  • The induction of phase II enzymes including quinone reductase [NAD(P)H dehydrogenase(quinone): NAD(P)H : (quinone acceptor) oxidoreductase, EC 1.6.99.2] is a major mechanism of whereby a large group of heterogeneous compounds prevent the toxic, mutagenic, and neoplastic effects of carcinogen. Using murine hepatoma cells(Hepalclc7 cells), quinone reductase(QR) inducers as the possible chemopreventive agents were screened from rice bran, wheat bran, soymilk residue, defatted soybean cake, defatted sesame and perilla residues. The 80% methanol extracts of defatted sesame and perilla residues induced quinone reductase significantly while the others did have little effect on the enzyme induction. Thin layer chromatography of the extracts showed that the fastest moving band(Rf=0.70) in the developing solvent of n-butanol : n-propanol : 2N ammonia(10 : 60 : 30) was responsible for the enzyme induction by the 80% methanol extracts of defatted sesame and perilla residues. Further identification of active component(s) is in progress.

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Potent Inhibition of Human Cytochrome P450 1 Enzymes by Dimethoxyphenylvinyl Thiophene

  • Lee, Sang-Kwang;Kim, Yongmo;Kim, Mie-Young;Kim, Sanghee;Chun, Young-Jin
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.199-205
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    • 2004
  • Cytochrome P450 (P450) 1 enzymes such as P450 1A1, 1A2, and 181 are known to be involved in the oxidative metabolism of various procarcinogens and are regarded as important target enzymes for cancer chemoprevention. Previously, several hydroxystilbene compounds were reported to inhibit P450 1 enzymes and were rated as candidate chemopreventive agents. In this study, we investigated the inhibitory effect of 2-[2-(3,5-dimethoxyphenyl)vinyl]-thiophene (DMPVT), produced from the chemical modification of oxyresveratrol, on the activities of P450 1 enzymes. The inhibitory potential by DMPVT on the P450 1 enzyme activity was evaluated with the Escherichia coli membranes of the recombinant human cytochrome P450 1A1, 1A2, or 1B1 coexpressed with human NADPH-P450 reductase. DMPVT significantly inhibited ethoxyresorufin O-deethylation (EROD) activities with $IC_{50}$ values of 61, 11, and 2 nM for 1A1, 1A2, and 1B1, respectively. The EROO activity in OMBA-treated rat lung microsomes was also significantly inhibited by OMPVT in a dose-dependent manner. The modes of inhibition by DMPVT were non-competitive for all three P450 enzymes. The inhibition of P450 1B1-mediated EROD activity by OMPVT did not show the irreversible mechanism-based effect. The loss of EROD activity in P450 1B1 with OMPVT incubation was not blocked by treatment with the trapping agents such as glutathione, N-acetylcysteine, or dithiothreitol. Taken together, the results suggested DMPVT to be a strong noncompetitive inhibitor of human P450 1 enzymes that should be considered as a good candidate for a cancer chemopreventive agent in humans.

CHEMOPREVENTIVE EFFECT OF GENISTEIN IN HAMSTER BUCCAL POUCH CARCINOGENESIS (Genistein이 햄스터 협낭 구강암 모델에 미치는 암예방 효과)

  • Kim, Young-Youn;Myoung, Hoon;Kim, Myung-Jin
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.2
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    • pp.135-141
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    • 2001
  • Recently, the consumption of soy products has been associated with low rates of hormone-dependent and hormone-independent cancers. Asians, who consume $20{\sim}50times$ more soy per capita than Americans, have lower incidence and death rates from breast and prostate cancer. Because soy contains the isoflavones genistein and daidzein (present as their glycosidic conjugates) at mg/g concentrations, it has been suggested that isoflavones might be acting as natural chemopreventive agents. During the 1980s several groups of investigators carried out experiments to test the effectiveness of soy in the diet in animal models of cancer. These studies reported a protective effect of soy; none showed that soy increased cancer risk. Genistein was shown to inhibit the growth of a wide variety of tumor cell types in culture. The purpose of this study was to evaluate the effects of genistein on the carcinogenesis induced by topical application of 0.5% 9, 10-dimethyl 1,2-benzanthracene (DMBA) on the hamster buccal pouch. 48 syrian hamsters were employed in this study, divided into experimental group and control. 24 animals (DMBA topical application group) had the right buccal pouch painted 3times weekly with 0.5% DMBA in mineral oil, 24 animals (genistein group) were supplied with 0.1mg genistein with DMBA topical application. 3 animals in the experimental group and control were sacrificed at serially each other week after experiments. Their buccal pouches were removed and routinely processed for microscopic examination. The results were as follows: 1. In DMBA topical application and genistein group, they showed carcinogenesis as time goes by experimental stage. 2. Genistein group was retarded in carcinogenesis related to the acanthosis, hyperkeratosis, epithelial dysplasia. 3. p53 immunohistochemical study showed that the p53 protein of genistein group was less expressed than that of the control group. Thus, it seems that genistein has chemopreventive effect on the carcinogenesis in the oral cavity, but further study is required to elucidate the anticancer mechanism of genistein.

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