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Harukuni Tokuda - One of the best experts on this subject based on the ideXlab platform.
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potential Cancer Chemopreventive and antiCancer constituents from the fruits of ficus hispida l f moraceae
Journal of Ethnopharmacology, 2018Co-Authors: Jie Zhang, Harukuni Tokuda, Wanfang Zhu, Worapong Kitdamrongtham, Aranya Manosroi, Jiradej Manosroi, Masahiko Abe, Toshihiro Akihisa, Feng FengAbstract:Abstract Ethnopharmacological relevance Ficus hispida L.f. (Moraceae) has been used as alternative for traditional medicine in the treatment of various ailments including Cancer-cure. The aim of this study was to evaluate the Cancer Chemopreventive and antiCancer activities of crude extracts of F. hispida, with the objective to screen the inhibition of Epstein–Barr virus early antigen, and cytotoxic active components, and provide foundation for potential applications of this promising medical plant. Materials and methods Compounds were isolated from the MeOH extract of F. hispida fruits, and their structure elucidation was performed on the basis of extensive spectroscopic analysis. The isolated compounds were evaluated for their inhibitory activities against the Epstein–Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells, and cytotoxic activities against human Cancer cell lines (HL60, A549, SKBR3, KB, Hela, HT29, and HepG2) and a normal cell (LO2) using MTT method. For the compound with potent cytotoxic activity, its apoptosis inducing activity was evaluated by the observation of ROS generation level expression, and membrane phospholipid exposure and DNA fragmentation in flow cytometry. The mechanisms of the apoptosis induction were analyzed by Western blotting. Results Nineteen compounds, 1–19, including two new isoflavones, 3′-formyl-5,7-dihydroxy-4′-methoxyisoflavone (2) and 5,7-dihydroxy-4′-methoxy-3′- (3-methyl-2-hydroxybuten-3-yl)isoflavone (3), were isolated from the MeOH extract of F. hispida fruits. Five compounds, isowigtheone hydrate (1), 2, 3, 9, and 19, showed potent inhibitory effects on EBV-EA induction with IC50 values in the range of 271–340 molar ratio 32 pmol−1 TPA. In addition, five phenolic compounds, 1–3, 10, and 13, exhibited cytotoxic activity against two or more cell lines (IC50 2.5–95.8 μM), as well as compounds 1 and 3 were also displayed high selectivity for LO2/HepG2 (SI 23.5 and 11.8, respectively), while the compound 1-induced ROS generation leads to activated caspases-3, −8, and −9 apoptotic process in HL60 cells. Conclusion This study has established that the MeOH extract of F. hispida fruits contains isoflavones, coumarins, caffeoylquinic acids, along with other compounds including phenolics and steroid glucoside as active principles, and has demonstrated that the chemical constituents of F. hispida may be valuable as potential Chemopreventive and antiCancer agents.
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melanogenesis inhibitory activity and Cancer Chemopreventive effect of glucosylcucurbic acid from shea vitellaria paradoxa kernels
Chemistry & Biodiversity, 2015Co-Authors: Jie Zhang, Harukuni Tokuda, Masahiro Kurita, Kodai Ebina, Motohiko Ukiya, Ken Yasukawa, Eliot T Masters, Naoto Shimizu, Momoko Akihisa, Feng FengAbstract:Two jasmonate derivatives, glucosylcucurbic acid (1) and methyl glucosylcucurbate (2), were isolated from the MeOH extract of defatted shea (Vitellaria paradoxa; Sapotaceae) kernels. These and their deglucosylated derivatives, cucurbic acid (3) and methyl cucurbate (4), were evaluated for their melanogenesis-inhibitory and Cancer Chemopreventive potencies. Compounds 1, 3, and 4 exhibited potent melanogenesis-inhibitory activities in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 melanoma cells. Western-blot analysis revealed that compounds 1 and 3 reduced the protein levels of MITF (=microphthalmia-associated transcription factor), tyrosinase, TRP-1 (=tyrosine-related protein 1), and TRP-2 mostly in a concentration-dependent manner. In addition, compound 1 exhibited inhibitory effects against EpsteinBarr virus early antigen (EBV-EA) activation induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, against TPA-induced inflammation in mice, and against skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter.
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total synthesis of plagiochin g and derivatives as potential Cancer Chemopreventive agents
ChemInform, 2015Co-Authors: Yu Zhao, Harukuni Tokuda, Xiaoming Yang, Yuehu Wang, Qian Shi, Susan L Morrisnatschke, Hongxiang Lou, Kuo Hsiung LeeAbstract:A new and efficient total synthesis has been developed to obtain plagiochin G (22), a macrocyclic bisbibenzyl, and four derivatives. The key 16-membered ring containing biphenyl ether and biaryl units was closed via an intramolecular SNAr reaction. All synthesized macrocyclic bisbibenzyls inhibited Epstein–Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells and, thus, are potential Cancer Chemopreventive agents.
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part i synthesis Cancer Chemopreventive activity and molecular docking study of novel quinoxaline derivatives
European Journal of Medicinal Chemistry, 2011Co-Authors: Shadia A Galal, Harukuni Tokuda, Ahmed S Abdelsamie, Nobutaka Suzuki, Akira Lida, Mahmoud Elhefnawi, Raghda A Ramadan, Mona H E Atta, Hoda El I DiwaniAbstract:The reaction of o-phenylene diamine and ethyl oxamate is reinvestigated and led to 3-aminoquinoxalin-2(1H)-one rather than benzimidazole-2-carboxamide as was previously reported. The structure of the obtained quinoxaline has been confirmed by X-ray. The anti-tumor activity of synthesized quinoxalines 1-21 has been evaluated by studying their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds 1-21, compounds 12, 8, 13, 18, 17 and 19, respectively, demonstrated strong inhibitory effects on the EBV-EA activation without showing any cytotoxicity and their effects being stronger than that of a representative control, oleanolic acid. Furthermore, compound 12 exhibited a remarkable inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. The result of the present investigation indicated that compound 12 might be valuable as a potent Cancer Chemopreventive agent. Moreover, the molecular docking into PTK (PDB: 1t46) has been done for lead optimization of the aforementioned compounds as potential PTK inhibitors.
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Chemopreventive activities of etodolac and oxyphenbutazone against mouse skin carcinogenesis
Bioorganic & Medicinal Chemistry Letters, 2010Co-Authors: Govind J Kapadia, Magnus A Azuine, Harukuni Tokuda, Nobutaka Suzuki, Yuuko ShigetaAbstract:Abstract Previous Cancer chemoprevention studies have demonstrated that the non-steroidal anti-inflammatory drugs (NSAIDs) can be effective in suppressing the development of various human malignancies. Recently we identified the possible anti-tumor promoting potentials of 14 new NSAIDs in the Epstein–Barr virus early antigen activation assay induced by 12- O -tetradecanoylphorbol-13-acetate (TPA). In this study we report the inhibition of 7,12-dimethylbenz (a) anthracene (DMBA) induced two-stage mouse skin carcinogenesis by etodolac (ETD), one of the most potent NSAIDs identified in our in vitro Cancer Chemopreventive screening of this group of drugs. Topical administration of ETD at a very low dose of 85 nmol showed a significant decrease in both tumor incidence and burden. This effect is also accompanied by a delay in the tumor latency period. Since ETD showed potent Chemopreventive activity in both in vitro and in vivo studies, it warrants prompt consideration for trial in humans as a potential Cancer Chemopreventive agent. We also investigated oxyphenbutazone (OPB) another commonly used NSAID for its Cancer Chemopreventive effect on peroxynitrite (PN) induced-TPA promoted skin tumors in the mouse. Following tumor initiation with 390 nmol of PN, the skin tumor promotion with 1.7 nmol of TPA was significantly inhibited by oral administration of 0.0025% OPB. The results demonstrate that OPB is a potent Cancer Chemopreventive agent in the highly sensitive in vivo mouse test model we used.
Ahng Tony Kong - One of the best experts on this subject based on the ideXlab platform.
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dietary glucosinolates sulforaphane phenethyl isothiocyanate indole 3 carbinol 3 3 diindolylmethane antioxidative stress inflammation nrf2 epigenetics epigenomics and in vivo Cancer Chemopreventive efficacy
Current Pharmacology Reports, 2015Co-Authors: Francisco Fuentes, Ximena Paredesgonzalez, Ahng Tony KongAbstract:Glucosinolates are a group of sulfur-containing glycosides found in many plant species, including cruciferous vegetables such as broccoli, cabbage, brussels sprouts, and cauliflower. Accumulating evidence increasingly supports the beneficial effects of dietary glucosinolates on overall health, including as potential anti-Cancer agents, because of their role in the prevention of the initiation of carcinogenesis via the induction of cellular defense detoxifying/antioxidant enzymes and their epigenetic mechanisms, including modification of the CpG methylation of Cancer-related genes, histone modification regulation and changes in the expression of miRNAs. In this context, the defense mechanism mediated by Nrf2-antioxidative stress and anti-inflammatory signaling pathways can contribute to cellular protection against oxidative stress and reactive metabolites of carcinogens. In this review, we summarize the Cancer Chemopreventive role of naturally occurring glucosinolate derivatives as inhibitors of carcinogenesis, with particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo human Cancer animal models.
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epigenetic modifications of nrf2 by 3 3 diindolylmethane in vitro in tramp c1 cell line and in vivo tramp prostate tumors
Aaps Journal, 2013Co-Authors: Tin Oo Khor, Constance Lay Lay Saw, Limin Shu, Kalung Cheung, Ying Huang, Ahng Tony KongAbstract:3,3′-diindolylmethane (DIM) is currently being investigated in many clinical trials including prostate, breast, and cervical Cancers and has been shown to possess antiCancer effects in several in vivo and in vitro models. Previously, DIM has been reported to possess Cancer Chemopreventive effects in prostate carcinogenesis in TRAMP mice; however, the in vivo mechanism is unclear. The present study aims to investigate the in vitro and in vivo epigenetics modulation of DIM in TRAMP-C1 cells and in TRAMP mouse model. In vitro study utilizing TRAMP-C1 cells showed that DIM suppressed DNMT expression and reversed CpG methylation status of Nrf2 resulting in enhanced expression of Nrf2 and Nrf2-target gene NQO1. In vivo study, TRAMP mice fed with DIM-supplemented diet showed much lower incidence of tumorigenesis and metastasis than the untreated control group similar to what was reported previously. DIM increased apoptosis, decreased cell proliferation and enhanced Nrf2 and Nrf2-target gene NQO1 expression in prostate tissues. Importantly, immunohistochemical analysis showed that DIM reduced the global CpG 5-methylcytosine methylation. Focusing on one of the early Cancer Chemopreventive target gene Nrf2, bisulfite genomic sequencing showed that DIM decreased the methylation status of the first five CpGs of the Nrf2 promoter region, corroborating with the results of in vitro TRAMP-C1 cells. In summary, our current study shows that DIM is a potent Cancer Chemopreventive agent for prostate Cancer and epigenetic modifications of the CpG including Nrf2 could be a potential mechanism by which DIM exerts its Chemopreventive effects.
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chemoprevention of familial adenomatous polyposis by natural dietary compounds sulforaphane and dibenzoylmethane alone and in combination in apcmin mouse
Cancer Research, 2007Co-Authors: Guoxiang Shen, Sujit Nair, Tin Oo Khor, Bandaru S Reddy, Moutuan Huang, Harold L Newmark, Ahng Tony KongAbstract:Cancer Chemopreventive agent sulforaphane (SFN) and dibenzoylmethane (DBM) showed antitumorigenesis effects in several rodent carcinogenesis models. In this study, we investigated the Cancer Chemopreventive effects and the underlying molecular mechanisms of dietary administration of SFN and DBM alone or in combination in the Apc Min/+ mice model. Male Apc Min/+ mice (12 per group) at age of 5 weeks were given control AIN-76A diet, diets containing 600 ppm SFN and 1.0% DBM, or a combination of 300 ppm SFN and 0.5% DBM for 10 weeks. Mice were then sacrificed, and tumor numbers and size were examined. Microarray analysis, Western blotting, ELISA, and immunohistochemical staining were done to investigate the underlying molecular mechanisms of Cancer Chemopreventive effects of SFN and DBM. Dietary administrations of SFN and DBM alone or in combination significantly inhibited the development of intestinal adenomas by 48% ( P = 0.002), 50% ( P = 0.001), and 57% ( P P = 0.016) and 60% ( P = 0.103), respectively, whereas the combination of SFN and DBM treatment blocked the colon tumor development ( P = 0.002). Both SFN and DBM treatments resulted in decreased levels of prostaglandin E 2 or leukotriene B 4 in intestinal polyps or apparently normal mucosa. Treatments also led to the inhibition of cell survival and growth-related signaling pathways (such as Akt and extracellular signal-regulated kinase) or biomarkers (such as cyclooxygenase-2, proliferating cell nuclear antigen, cleaved caspases, cyclin D1, and p21). In conclusion, our results showed that both SFN and DBM alone as well as their combination are potent natural dietary compounds for chemoprevention of gastrointestinal Cancers. [Cancer Res 2007;67(20):9937–44]
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Natural dietary anti-Cancer Chemopreventive compounds: redox-mediated differential signaling mechanisms in cytoprotection of normal cells versus cytotoxicity in tumor cells
Acta Pharmacologica Sinica, 2007Co-Authors: Sujit Nair, Ahng Tony KongAbstract:Many dietary phytochemicals exhibit health-beneficial effects including prevention of diseases such as Cancer, as well as neurological, cardiovascular, inflammatory, and metabolic diseases. Evolutionarily, herbivorous and omnivorous animals have been ingesting plants. This interaction between “animal-plant” ecosystems has resulted in an elaborate system of detoxification and defense mechanisms evolved by animals including humans. Mammalian cells, including human cells, respond to these dietary phytochemicals by “non-classical receptor sensing” mechanisms of electrophilic chemical-stress typified by “thiol-modulated” cellular signaling events primarily leading to the gene expression of pharmacologically beneficial effects, but sometimes unwanted cytotoxicity also. Our laboratory has been studying two groups of dietary phytochemical Cancer-Chemopreventive compounds (isothiocyanates and polyphenols), which are effective in chemical-induced, as well as genetically-induced, animal carcinogenesis models. These compounds typically generate “cellular stress” and modulate gene expression of phase II detoxifying/antioxidant enzymes. Electrophiles, reactive oxygen species, and reactive nitrogen species are known to act as second messengers in the modulation of many cellular signaling pathways leading to gene expression changes and pharmacological responses. Redox-sensitive transcription factors such as nuclear factor-E2-related factor 2 (Nrf2), AP-1, NF-κB, to cite a few examples, sense and transduce changes in the cellular redox status and modulate gene expression responses to oxidative and electrophilic stresses, presumably via sulfhydryl modification of critical cysteine residues found on these proteins and/or other upstream redox-sensitive molecular targets. In the current review, we will explore dietary Cancer Chemopreventive phytochemicals, discuss the link between oxidative/electrophilic stresses and the redox circuitry, and consider different redox-sensitive transcription factors. We will also discuss the kelch-like erythroid Cap‘n’ Collar homologue-associated protein 1 (Keap1)-Nrf2 axis in redox signaling of induction of phase II detoxifying/antioxidant defense mechanisms, an important target and preventive strategy for normal cells against carcinogenesis, and the converse inhibition of cell growth/inflammatory signaling pathways that would confer therapeutic intervention in many types of Cancers. Finally, we will summarize the Nrf2 paradigm in gene expression, the pharmacotoxicogenomic relevance of redox-sensitive Nrf2, and the redox regulation of cell death mechanisms.
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gene expression profiles induced by Cancer Chemopreventive isothiocyanate sulforaphane in the liver of c57bl 6j mice and c57bl 6j nrf2 mice
Cancer Letters, 2006Co-Authors: Guoxiang Shen, Jefferson Y Chan, Mohit Jain, Tin Oo Khor, Avantika Gopalkrishnan, Wen Lin, Bandaru S Reddy, Ahng Tony KongAbstract:Abstract Sulforaphane (SFN) is a potent and promising naturally occurring dietary Cancer Chemopreventive compound that exerts its Cancer protective effects by the induction of genes including cellular defensive genes such as phase II detoxifying and antioxidant enzymes. This gene induction primarily occurs via the transcription factor Nrf2 acting on the antioxidant response element (ARE) located at the 5′-flanking region of these genes. In the present study, transcriptional expression profiles of the livers obtained from the nrf2 wild-type mice and the nrf2 knockout (−/−) mice after treatments with vehicle or SFN at 3 and 12 h were generated using the Affymetrix 39 K oligonucleotide microarray. The Nrf2-dependent, SFN-inducible genes were identified which include detoxification phase I, II drug metabolizing enzymes and phase III transporters. Unexpected clusters of genes include genes for heat shock proteins (HSP), ubiquitin/26 S proteasome subunits, and lipid metabolism genes. Collectively, SFN increases the expression of genes through the Nrf2 signaling pathway that directly detoxify exogenous toxins/carcinogens or endogenous reactive oxygen species, and genes involved in the recognition and repair/removal of damaged proteins, which could provide secondary protection against DNA or protein damage that enhance cell survival.
Andreas J Gescher - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics and metabolism of the putative Cancer Chemopreventive agent cyanidin 3 glucoside in mice
Cancer Chemotherapy and Pharmacology, 2009Co-Authors: Timothy H Marczylo, Karen Brown, William P Steward, Darren N Cooke, Andreas J GescherAbstract:Purpose Cyanidin-3-glucoside (C3G), an anthocyanin component of fruits and berries, possesses Cancer Chemopreventive properties in mouse models of carcinogenesis. Its pharmacokinetics and metabolism in mice have hitherto not been studied.
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do anthocyanins and anthocyanidins Cancer Chemopreventive pigments in the diet merit development as potential drugs
Cancer Chemotherapy and Pharmacology, 2009Co-Authors: Sarah Thomasset, Nicole Teller, Hong Cai, Doris Marko, David P Berry, William P Steward, Andreas J GescherAbstract:Anthocyanins, plant pigments in fruits and berries, have been shown to delay Cancer development in rodent models of carcinogenesis, especially those of the colorectal tract. Anthocyanins and anthocyanidins, their aglycons, especially cyanidin and delphinidin, have been subjected to extensive mechanistic studies. In cells in vitro, both glycosides and aglycons engage an array of anti-oncogenic mechanisms including anti-proliferation, induction of apoptosis and inhibition of activities of oncogenic transcription factors and protein tyrosine kinases. Anthocyanins and anthocyanidins exist as four isomers, interconversion between which depends on pH, temperature and access to light. Anthocyanidins are much more prone to avid chemical decomposition than the glycosides, and they only survive for minutes in the biophase. These pharmaceutical issues are very important determinants of the suitability of these flavonoids for potential development as Cancer Chemopreventive drugs, and they have hitherto not received adequate attention. In the light of their robust Cancer Chemopreventive efficacy in experimental models and their superior stability as compared to that of the aglycons, the anthocyanins seem much more suitable for further drug development than their anthocyanidin counterparts.
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phase i dose escalation pharmacokinetic study in healthy volunteers of resveratrol a potential Cancer Chemopreventive agent
Cancer Epidemiology Biomarkers & Prevention, 2007Co-Authors: David J. Boocock, Ketan R Patel, Tristan D Booth, Marjorie Perloff, Guy Faust, Anna M Schinas, Victoria Brown, Murray P Ducharme, Jenna A.e. Crowell, Andreas J GescherAbstract:The red grape constituent resveratrol possesses Cancer Chemopreventive properties in rodents. The hypothesis was tested that, in healthy humans, p.o. administration of resveratrol is safe and results in measurable plasma levels of resveratrol. A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or 5 g) was conducted in 10 healthy volunteers per dose level. Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-tandem mass spectrometry and quantitated by high-performance liquid chromatography-UV. Consumption of resveratrol did not cause serious adverse events. Resveratrol and six metabolites were recovered from plasma and urine. Peak plasma levels of resveratrol at the highest dose were 539 ± 384 ng/mL (2.4 μmol/L, mean ± SD; n = 10), which occurred 1.5 h post-dose. Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold higher. The area under the plasma concentration curve (AUC) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol. Urinary excretion of resveratrol and its metabolites was rapid, with 77% of all urinary agent-derived species excreted within 4 h after the lowest dose. Cancer Chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 μmol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with Cancer Chemopreventive efficacy. However, the high systemic levels of resveratrol conjugate metabolites suggest that their Cancer Chemopreventive properties warrant investigation. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1246–52)
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phase i dose escalation pharmacokinetic study in healthy volunteers of resveratrol a potential Cancer Chemopreventive agent
Cancer Epidemiology Biomarkers & Prevention, 2007Co-Authors: David J. Boocock, Ketan R Patel, Tristan D Booth, Marjorie Perloff, Guy Faust, Anna M Schinas, Victoria Brown, Murray P Ducharme, Jenna A.e. Crowell, Andreas J GescherAbstract:The red grape constituent resveratrol possesses Cancer Chemopreventive properties in rodents. The hypothesis was tested that, in healthy humans, p.o. administration of resveratrol is safe and results in measurable plasma levels of resveratrol. A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or 5 g) was conducted in 10 healthy volunteers per dose level. Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-tandem mass spectrometry and quantitated by high-performance liquid chromatography-UV. Consumption of resveratrol did not cause serious adverse events. Resveratrol and six metabolites were recovered from plasma and urine. Peak plasma levels of resveratrol at the highest dose were 539 +/- 384 ng/mL (2.4 micromol/L, mean +/- SD; n = 10), which occurred 1.5 h post-dose. Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold higher. The area under the plasma concentration curve (AUC) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol. Urinary excretion of resveratrol and its metabolites was rapid, with 77% of all urinary agent-derived species excreted within 4 h after the lowest dose. Cancer Chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 micromol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with Cancer Chemopreventive efficacy. However, the high systemic levels of resveratrol conjugate metabolites suggest that their Cancer Chemopreventive properties warrant investigation.
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comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine
Cancer Chemotherapy and Pharmacology, 2007Co-Authors: Timothy H Marczylo, William P Steward, Darren N Cooke, Richard D Verschoyle, Paolo Morazzoni, Andreas J GescherAbstract:Purpose Curcumin, a major constituent of the spice turmeric, suppresses expression of the enzyme cyclooxygenase 2 (Cox-2) and has Cancer Chemopreventive properties in rodents. It possesses poor systemic availability. We explored whether formulation with phosphatidylcholine increases the oral bioavailability or affects the metabolite profile of curcumin.
Masataka Itoigawa - One of the best experts on this subject based on the ideXlab platform.
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Cancer Chemopreventive activity of terpenoid coumarins from ferula species
Planta Medica, 2008Co-Authors: Mehrdad Iranshahi, Harukuni Tokuda, Hiroshi Furukawa, Chihiro Ito, Farhad Kalategi, Ramin Rezaee, Ahmad Reza Shahverdi, Masataka ItoigawaAbstract:Abstract Several naturalproducts havebeenfoundtohavestudy, we carried out a primary screening of tenterpenoid coumarins isolated from plants of the Ferula species, examining their possible inhibito-ry effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12- O -tetradeca-noylphorbol 13-acetate(TPA) in Raji cells. Aurap-tene (7-geranyloxycoumarin, 1 ) and umbellipre-nin (7-farnesyloxycoumarin, 2 ) were found tosignificantly inhibit EBV-EA activation and pre-served the high viability of Raji cells, suggestingthat they might be valuable anti-tumor-promot-ing agents (IC 50 8.3 and 9.1nM, respectively).Ourfindingsrevealedthatthepresenceofapren-yl moiety in the terpenoid coumarins plays animportant role in anti-tumor promoting activityas previously reported for xanthones, coumarins,flavonoids and phenylpropanoids. Supporting information available online athttp://www.thieme-connect.de/ejournals/toc/plantamedica Iranshahi Met al. Cancer Chemopreventive Activity… Planta Med 2008; 74: 147–150
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Cancer Chemopreventive activity of rotenoids from derris trifoliata
Planta Medica, 2004Co-Authors: Masataka Itoigawa, Naoki Kojima, Hiroshi FurukawaAbstract:A study of the chemical constituents of the stems of Derris trifoliata Lour. (Leguminosae) led to the isolation and identification of one new rotenoid, 6aα,12aα-12a-hydroxyelliptone (3), together with five other known rotenoids. In a search for novel Cancer Chemopreventive agents (anti-tumor promoters), we carried out a primary screening of five of the rotenoids isolated from the plant for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. The inhibitory activity of 3 was found to be equivalent to that of β-carotene without any cytotoxicity. Deguelin (4) and α-toxicarol (5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. This investigation indicated that rotenoids might be valuable anti-tumor promoters.
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Cancer Chemopreventive activity of acridone alkaloids on epstein barr virus activation and two stage mouse skin carcinogenesis
Cancer Letters, 2003Co-Authors: Fumio Enjo, Masataka Itoigawa, Harukuni Tokuda, Hoyoku Nishino, Chihiro Ito, Hiroshi FurukawaAbstract:Seventeen acridone alkaloids isolated from the Rutaceous plants were tested for their inhibitory activities against Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. Some prenylated acridones were found to have remarkably potent activities. 1,3-Dihydroxy-10-methyl-2,4-diprenylacridone (18) as synthesized according to these results in vitro, exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The result of the present investigation indicated that some of these acridone alkaloids may be potentially valuable Cancer Chemopreventive agents.
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chemical constituents of calophyllum brasiliense 2 structure of three new coumarins and Cancer Chemopreventive activity of 4 substituted coumarins
Journal of Natural Products, 2003Co-Authors: Chihiro Ito, Fumio Enjo, Masataka Itoigawa, Harukuni Tokuda, Yoshitaka Mishina, Valdir Cechinel Filho, Hiroshi FurukawaAbstract:Continuing our search for Cancer Chemopreventive agents from natural sources, we examined constituents of the stem bark of Calophyllum brasiliense. Three new 4-substituted coumarins named brasimarins A (2), B (3), and C (4) were isolated and characterized, along with 11 known coumarins belonging to the calanolides or inophyllums. We also discuss the inhibitory effects of these coumarins on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells.
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Cancer Chemopreventive activity of flavanones on epstein barr virus activation and two stage mouse skin carcinogenesis
Cancer Letters, 2002Co-Authors: Masataka Itoigawa, Harukuni Tokuda, Eiichiro Ichiishi, Hoyoku Nishino, Chihiro Ito, Motoharu Juichi, Toshihiro Nobukuni, Hiroshi FurukawaAbstract:To search for possible Cancer Chemopreventive agents from natural sources, we performed primary screening of ten flavanones isolated from plants belonging to Rutaceae and Leguminosae by examining their possible inhibitory effects on Epstein-Barr virus (EBV) early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All of the flavanones tested in this study showed inhibitory activity against EBV, without showing any cytotoxicity. Amorilin (3), which has three prenyl (3-methyl-2-butenyl) side-chains in the molecule, showed the most potent activity. Furthermore, lupinifolin (5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These results indicate that some of these prenylated flavanones might be valuable as potential Cancer Chemopreventive agents (anti-tumor promoters).
Hiroshi Furukawa - One of the best experts on this subject based on the ideXlab platform.
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Cancer Chemopreventive activity of terpenoid coumarins from ferula species
Planta Medica, 2008Co-Authors: Mehrdad Iranshahi, Harukuni Tokuda, Hiroshi Furukawa, Chihiro Ito, Farhad Kalategi, Ramin Rezaee, Ahmad Reza Shahverdi, Masataka ItoigawaAbstract:Abstract Several naturalproducts havebeenfoundtohavestudy, we carried out a primary screening of tenterpenoid coumarins isolated from plants of the Ferula species, examining their possible inhibito-ry effects on Epstein-Barr virus early antigen(EBV-EA) activation induced by 12- O -tetradeca-noylphorbol 13-acetate(TPA) in Raji cells. Aurap-tene (7-geranyloxycoumarin, 1 ) and umbellipre-nin (7-farnesyloxycoumarin, 2 ) were found tosignificantly inhibit EBV-EA activation and pre-served the high viability of Raji cells, suggestingthat they might be valuable anti-tumor-promot-ing agents (IC 50 8.3 and 9.1nM, respectively).Ourfindingsrevealedthatthepresenceofapren-yl moiety in the terpenoid coumarins plays animportant role in anti-tumor promoting activityas previously reported for xanthones, coumarins,flavonoids and phenylpropanoids. Supporting information available online athttp://www.thieme-connect.de/ejournals/toc/plantamedica Iranshahi Met al. Cancer Chemopreventive Activity… Planta Med 2008; 74: 147–150
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Cancer Chemopreventive activity of rotenoids from derris trifoliata
Planta Medica, 2004Co-Authors: Masataka Itoigawa, Naoki Kojima, Hiroshi FurukawaAbstract:A study of the chemical constituents of the stems of Derris trifoliata Lour. (Leguminosae) led to the isolation and identification of one new rotenoid, 6aα,12aα-12a-hydroxyelliptone (3), together with five other known rotenoids. In a search for novel Cancer Chemopreventive agents (anti-tumor promoters), we carried out a primary screening of five of the rotenoids isolated from the plant for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) in Raji cells. The inhibitory activity of 3 was found to be equivalent to that of β-carotene without any cytotoxicity. Deguelin (4) and α-toxicarol (5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. This investigation indicated that rotenoids might be valuable anti-tumor promoters.
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Cancer Chemopreventive activity of acridone alkaloids on epstein barr virus activation and two stage mouse skin carcinogenesis
Cancer Letters, 2003Co-Authors: Fumio Enjo, Masataka Itoigawa, Harukuni Tokuda, Hoyoku Nishino, Chihiro Ito, Hiroshi FurukawaAbstract:Seventeen acridone alkaloids isolated from the Rutaceous plants were tested for their inhibitory activities against Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. Some prenylated acridones were found to have remarkably potent activities. 1,3-Dihydroxy-10-methyl-2,4-diprenylacridone (18) as synthesized according to these results in vitro, exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The result of the present investigation indicated that some of these acridone alkaloids may be potentially valuable Cancer Chemopreventive agents.
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chemical constituents of calophyllum brasiliense 2 structure of three new coumarins and Cancer Chemopreventive activity of 4 substituted coumarins
Journal of Natural Products, 2003Co-Authors: Chihiro Ito, Fumio Enjo, Masataka Itoigawa, Harukuni Tokuda, Yoshitaka Mishina, Valdir Cechinel Filho, Hiroshi FurukawaAbstract:Continuing our search for Cancer Chemopreventive agents from natural sources, we examined constituents of the stem bark of Calophyllum brasiliense. Three new 4-substituted coumarins named brasimarins A (2), B (3), and C (4) were isolated and characterized, along with 11 known coumarins belonging to the calanolides or inophyllums. We also discuss the inhibitory effects of these coumarins on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells.
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Cancer Chemopreventive activity of flavanones on epstein barr virus activation and two stage mouse skin carcinogenesis
Cancer Letters, 2002Co-Authors: Masataka Itoigawa, Harukuni Tokuda, Eiichiro Ichiishi, Hoyoku Nishino, Chihiro Ito, Motoharu Juichi, Toshihiro Nobukuni, Hiroshi FurukawaAbstract:To search for possible Cancer Chemopreventive agents from natural sources, we performed primary screening of ten flavanones isolated from plants belonging to Rutaceae and Leguminosae by examining their possible inhibitory effects on Epstein-Barr virus (EBV) early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All of the flavanones tested in this study showed inhibitory activity against EBV, without showing any cytotoxicity. Amorilin (3), which has three prenyl (3-methyl-2-butenyl) side-chains in the molecule, showed the most potent activity. Furthermore, lupinifolin (5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These results indicate that some of these prenylated flavanones might be valuable as potential Cancer Chemopreventive agents (anti-tumor promoters).
