• Title, Summary, Keyword: tumor promotion

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Isolation of a Quinone-rich Fraction from Ardisia crispa Roots and its Attenuating Effects on Murine Skin Tumorigenesis

  • Yeong, Looi Ting;Hamid, Roslida Abdul;Yazan, Latifah Saiful;Khaza'ai, Huzwah
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2301-2305
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    • 2013
  • Ardisia crispa (Family: Myrsinaceae) is an evergreen, fruiting shrub that has been traditionally used as folklore medicine. Despite a scarcity of research publications, we have succeeded in showing suppressive effects on murine skin papillomagenesis. In extension, the present research was aimed at determining the effect of a quinone-rich fraction (QRF) isolated from the same root hexane extract on both initiation and promotion stages of carcinogenesis, at the selected dose of 30 mg/kg. Mice (groups I-IV) were initiated with a single dose of 7,12-dimethylbenz(${\alpha}$)anthracene (DMBA, $100{\mu}g/100{\mu}l$) followed by repeated promotion of croton oil (1%) twice weekly for 20 weeks. In addition, group I (anti-initiation) received QRF 7 days before and after DMBA; group II (anti-promotion) received QRF 30 minutes before each croton oil application; group III (anti-initiation/promotion) was treated with QRF as a combination of group I and II. A further two groups served as vehicle control (group V) and treated control (group VI). As carcinogen control, group IV showed the highest tumor volume ($8.79{\pm}5.44$) and tumor burden ($3.60{\pm}1.17$). Comparatively, group III revealed only 20% of tumor incidence, tumor burden ($3.00{\pm}1.00$) and tumor volume ($2.40{\pm}1.12$), which were significantly different from group IV. Group II also showed significant reduction of tumor volume (3.11), tumor burden (3.00) and tumor incidence (11.11%), along with prominent increase of latency period of tumor formation (week 12). Group I, nonetheless, demonstrated marked increment of tumor incidence by 40% with prompted latency period of tumor formation (week 7). No tumor formation was observed in groups V and VI. This study provided clear evidence of inhibitory effects of QRF during promotion period which was in agreement with our previous findings. The mechanism(s) underlying such effects have yet to be elucidated.

Control and Mechanism of Tumor Promotion in UV-Carcinogenesis

  • Ueda, Masato;Budiyanto, Arief;Ashida, Masashi;Bito, Toshinori;Ichihashi, Masamitsu
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.221-224
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    • 2002
  • Carcinogenesis can be theoretically divided to intiation step and promotion step. Intiation associates with genetic alterations including p53 tumor suppressor gene and ras oncogene. Promotion involves in clonal expansion of of an initiated cell by epigenetic mechanism, mainly through signal transduction and gene expression. Ultraviolet light (UV) acts as both initiator and promoter. Initiation is closely related with DNA damage induced by UV, including cyclobutane pyrimidine dimers, (6-4) photoproducts and 8-hydroxy-2'-deoxyguanosine. Cyclobutane pyrimidine dimers and (6-4) photoproducts are directly induced by UV, while 8-hydroxy-2'-deoxyguanosine is induced indirectly by the reactive oxygen species. Because initiation is an irreversal genetic event, while promotion is a reversal and epigenetic event, to know the molecular mechanisms of tumor promotion in UV-carcinogenesis is crucial to develop preventive medicine and suppress UV-carcinogenesis. Because ROS is also involved in signal transduction of the cell, anti-oxidant could be the good candidate of anti-promoting agent. Here, we describe the suppressive effect of UV-carcinogenesis by various anti-oxidant including olive oil. In addition, we discuss about the mechanism of UVB-induced expression of cyclooxygenase-2, which might be a representative molecule involved in promotion of UV-carcinogenesis.

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Elucidation of Anti-tumor Initiator and Promoter Derived from Seaweed-3 : Anti-tumor Promoters of Ecklonia stolonifera Extracts (해조류 중의 anti-tumor initiator 및 promoter의 해석-3 : 곰피 추출물중의 발암 promotion억제 인자)

  • PARK Young-Beom;KIM In-Soo;YOO Sung-Jae;AHN Jong-Khan;LEE Tae-Gee;PARK Douck-Chon;KIM Seon-Bong
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.31 no.4
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    • pp.587-593
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    • 1998
  • To elucidate anti-tumor promoter from seaweed, the anti-tumor promoting activity of Ecklonia stolonifera, Undaria pinnatifida and Laminaria japonica extracts were determined by Epstein-Barr virus (EBV)-early antigen (EA) induction caused by a tumor promoter, teleocidin B-4. The methanol extracts of seaweed were subsequently fractionated with diethyl ether, distilled water, chloroform and ethyl acetate. Among the solvent fractions tested, chloroform and ethyl acetate fraction of E. stolonifera showed a high anti-tumor promoting activity at the levels of 88.0 and $85.9\%$ by the addition of 20 ${\mu}g/m{\ell}$, respectively. To characterize anti-tumor promoters from solvent fractions of E. stolonifera, the effects of phenols, chlorophyll derivatives and carotenoids on the anti-tumor promoting activity were investigated. Phenols, such as bromophenol and phloroglucinol showed anti-tumor promoting activity of $57\~66\%$ at 20 ${\mu}g/m{\ell}$. Pigments, such as chlorophylls and carotenoids exerted high anti-tumor promoting activities. Chlorophyll a and pheophorbide a exhibited the activity of $77.4\%$ and $66.6\%$ at 5${\mu}M/m{\ell}$, respectively. The active compounds of carotenoids were tentatively identified as lutein and $\alpha-cryptoxanthin$ from the profiles of visible spectra and R_f value of their authentic compounds, and showed anti-tumor promoting activities of $76.9\%$ and $84.4\%$ at dose of 20 ${\mu}g/m{\ell}$, respectively.

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Induction of Mouse Epidermal ODC by TPA and Inhibition by Plant Flavonoids, in Skin Tumor Promotion (다단계 발암과정 중 Promotion 단계에서의 TPA에 의한 Mouse Epidermal ODC의 유도 및 약물에 의한 차단효과)

  • 김미경;장일식;정문호
    • Journal of Environmental Health Sciences
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    • v.19 no.3
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    • pp.64-73
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    • 1993
  • The study was conducted to investigate the mechanism of tumor promotion as the time courses and the doses of promoter, and the effect of plant fiavonoids on the TPA-induced ODC responses. The results are summarized as follows: 1. A single, toppical application of 17 nmole of the potent tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate, resulted in an induction of mouse epidermal Ornithine Decarboxylase with a peak at 5 hours after treatment and maximized 5.1 times as large as ODC activities of control. 2. Dose-response curve indicated that the tumor promotion increases proportionally between 1.7 and 170 nmole of TPA. This dose dependency relationship indicated that the ability of TPA to stimulate ODC is linked its ability to promote tumors. 3. Naturally occurring plant fiavonoids with anticarcinogenic and antipromotional activities were tested for their abilities to inhibit ODC response induced by skin tumor promoter TPA. Intra peritoneal administration of fiavonoids compounds (rutin, naphthofiavone, baicalein, quercitrin) and herbal drugs (sophorae rios, crataegi fructus, armeniacae semen) inhibited 17 nmole TPA-induced ODC activities in mouse epidermis in vivo.

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Chemopreventive Potential of Annona Muricata L Leaves on Chemically-Induced Skin Papillomagenesis in Mice

  • Hamizah, Sulaiman;Roslida, A.H.;Fezah, O.;Tan, K.L.;Tor, Y.S.;Tan, C.I.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2533-2539
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    • 2012
  • Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(${\alpha}$)anthracene (DMBA 100ug/100ul acetone) and promotion by repeated application of croton oil (1% in acetone/twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in theAMLE-treated group. Interestingly, At 100 and 300 mg/kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.

Targeting the Transforming Growth Factor-β Signaling in Cancer Therapy

  • Sheen, Yhun Yhong;Kim, Min-Jin;Park, Sang-A;Park, So-Yeon;Nam, Jeong-Seok
    • Biomolecules & Therapeutics
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    • v.21 no.5
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    • pp.323-331
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    • 2013
  • TGF-${\beta}$ pathway is being extensively evaluated as a potential therapeutic target. The transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway has the dual role in both tumor suppression and tumor promotion. To design cancer therapeutics successfully, it is important to understand TGF-${\beta}$ related functional contexts. This review discusses the molecular mechanism of the TGF-${\beta}$ pathway and describes the different ways of tumor suppression and promotion by TGF-${\beta}$. In the last part of the review, the data on targeting TGF-${\beta}$ pathway for cancer treatment is assessed. The TGF-${\beta}$ inhibitors in pre-clinical studies, and Phase I and II clinical trials are updated.

An Arachidonic Acid Metabolizing Enzyme, 8S-Lipoxygenase, in Mouse Skin Carcinogenesis

  • Kim Eun-Jung
    • Nutritional Sciences
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    • v.9 no.3
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    • pp.212-226
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    • 2006
  • The involvement of arachidonic acid (AA) metabolizing enzyme, lipoxygenase (LOX), in the development of particular tumors in humans has gradually been acknowledged and LOX has emerged as a novel target to prevent or treat human cancers. In the mouse skin carcinogenesis model, which provides an excellent model to study multistage nature of human cancer development, many studies have shown that some of the LOXs are constitutively upregulated in their expression. Moreover, application of LOX inhibitors effectively reduced tumor burdens, which implicates the involvement of LOX in mouse skin tumor development as well. 8S-LOX is a recently cloned LOX, which is specifically expressed in mouse skin after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment but not in normal skin. Unlike other members of the LOX 'family' expressed in mouse skin, this TPA-induced expression of 8S-LOX is prominent only in the skin of the TPA tumor promotion-sensitive strains of mice (SENCAR, CD-1, and NMRI) but not in the promotion-resistant C57BL/6J mice. This is a very unique phenomenon among strains of mice. Constitutive upregulation of 8S-LOX was also found in early stage papillomas and the expression was gradually reduced as the tumors became malignant. Based on these observations, it has been thought that 8S-LOX is involved in TPA-induced tumor promotion as well as in tumor conversion from papillomas to carcinomas. In accordance with this hypothesis, several studies have suggested possible roles of 8S-hydroxyeicosatetraenoic acid (HETE), an AA metabolite of 8S-LOX, in mouse skin tumor development. A clastogenic activity of 8S-HETE was demonstrated in primary keratinocytes and a close correlation between the levels of etheno-DNA adducts and 8S-HETE during skin carcinogenesis was also reported. On the other hand, it has been reported that 8S-LOX protein expression is restricted to a differentiated keratinocyte compartment Moreover, reported findings on the ability of 8S-HETE to cause keratinocyte differentiation appear to be contrary to the procarcinogenic features of the 8S-LOX expression, presenting a question as to the role of 8S-LOX during mouse skin carcinogenesis. In this review, molecular and biological features of 8S-LOX as well as current views on the functional role of 8S-LOX/8S-HETE during mouse skin carcinogenesis are presented.

Amelioration of 1,2 Dimethylhydrazine (DMH) Induced Colon Oxidative Stress, Inflammation and Tumor Promotion Response by Tannic Acid in Wistar Rats

  • Hamiza, Oday O.;Rehman, Muneeb U.;Tahir, Mir;Khan, Rehan;Khan, Abdul Quaiyoom;Lateef, Abdul;Ali, Farrah;Sultana, Sarwat
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4393-4402
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    • 2012
  • Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changes and expression of early molecular markers of inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons of Wistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-${\alpha}$ (p<0.001) release. It could be concluded from our results that TA markedly protects against chemically induced colon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.

In vitro Inhibitory Effect of Colored Rice Bran Extracts Carcinogenicity (유색미 쌀겨추출물의 in vitro의 발암 억제효과)

  • Kang, Mi-Young;Nam, Seok-Hyun
    • Applied Biological Chemistry
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    • v.40 no.4
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    • pp.307-312
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    • 1997
  • As a preliminary experiment to investigate the antitumor activity of colored rice in vivo, inhibitory effect of solvent extracts from colored rice brans on DNA strand scission and tumor promotion was examined in vitro. Two colored rice cultivars, Sanghaehyanghyulla and Suwon 415 were compared with Chuchung as a control. The antimutagenic activity of each rice cultivars increased in order of Chuchung

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