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Hoyoku Nishino - One of the best experts on this subject based on the ideXlab platform.

  • cancer preventive agents part 8 chemopreventive effects of stevioside and related compounds
    Bioorganic & Medicinal Chemistry, 2009
    Co-Authors: Midori Takasaki, Junko Takayasu, Hoyoku Nishino, Takao Konoshima, Harukuni Tokuda, Mutsuo Kozuka, Masazumi Miyakoshi, Kenji Mizutani
    Abstract:

    Abstract In a search for potential cancer chemopreventive agents from natural resources, stevioside ( 1 ), a sweetener, and six related compounds, including two aglycones steviol ( 6 ) and isosteviol ( 7 ), were screened in an in vitro assay for inhibitory effects on Epstein–Barr virus Early Antigen activation. Compounds 1 , 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[ a ]anthracene (DMBA) and 12- O -tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of these three compounds were greater than that of glycyrrhizin. Furthermore, these three compounds significantly inhibited mouse skin carcinogenesis initiated by peroxynitrite and promoted by TPA. Their activities were comparable to that of curcumin. These results suggested that 1 , as well as 6 and 7 , could be valuable as chemopreventive agents for chemical carcinogenesis.

  • new antitumor sesquiterpenoids from santalum album of indian origin
    Tetrahedron, 2006
    Co-Authors: Tsutomu Hatano, Junko Takayasu, Hoyoku Nishino, Harukuni Tokuda, Takahisa Machiguchi, Takashi Yoshida
    Abstract:

    Abstract Three new campherenane-type (1, 4, 7) and three new santalane-type (9, 11, 12) sesquiterpenoids, and two aromatic glycosides (21, 22) together with 12 known metabolites including α,β-santalols (14, 18), (E)-α,β-santalals (15, 19), α,β-santaldiols (16, 20), α-santalenoic acid (17), and vanillic acid 4-O-neohesperidoside were isolated from Santalum album chips of Indian origin. The structures of the new compounds, including absolute configurations, were elucidated by 1D- and 2D-NMR spectroscopic and chemical methods. The antitumor promoting activity of these isolates along with several neolignans previously isolated from the same source was evaluated for both in vitro Epstein–Barr virus Early Antigen (EBV-EA) activation and in vivo two-stage carcinogenesis assays. Among them, compound 1 exhibited a potent inhibitory effect on EBV-EA activation, and also strongly suppressed two-stage carcinogenesis on mouse skin.

  • cancer preventive agents part 5 anti tumor promoting effects of coumarins and related compounds on epstein barr virus activation and two stage mouse skin carcinogenesis
    Pharmaceutical Biology, 2006
    Co-Authors: Madoka Suzuki, Hoyoku Nishino, Harukuni Tokuda, Mutsuo Kozuka, Kyoko Nakagawagoto, Seikou Nakamura, Susan L Morrisnatschke, Kuo Hsiung Lee
    Abstract:

    AbstractA series of coumarins and related compounds were synthesized and screened as potential anti-tumor-promoting agents by examining the ability of the compound to inhibit Epstein-Barr virus Early Antigen (EBV-EA) activation induced by 12-O.-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The most promising compound in this in vitro. assay, 7,8-di(3-methyl-2-butenyloxy)coumarin (17), showed confirmed chemopreventive activity in an in vivo. two-stage assay of mouse skin tumors (DMBA/TPA). This investigation also confirmed an important role for the prenyl moiety, and, possibly, for the dimethylpyran substructure, on the anti-tumor-promoting activity.

  • cancer chemopreventive activity of rotenoids from derris trifoliata
    Planta Medica, 2004
    Co-Authors: Masataka Itoigawa, Junko Takayasu, Hoyoku Nishino, Naoki Kojima, Hiroshi Furukawa
    Abstract:

    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.

  • cancer chemopreventive effect of phenothiazines and related tri heterocyclic analogues in the 12 o tetradecanoylphorbol 13 acetate promoted epstein barr virus Early Antigen activation and the mouse skin two stage carcinogenesis models
    Pharmacological Research, 2004
    Co-Authors: Magnus A Azuine, Junko Takayasu, Fumio Enjyo, Teruo Mukainaka, Hoyoku Nishino, Takao Konoshima, Harukuni Tokuda, Govind J Kapadia
    Abstract:

    Abstract In continuation of our search for novel agents, we have investigated 29 phenothiazines and related tri-heterocyclic compounds as potential cancer chemopreventive agents in a short-term in vitro assay of Epstein-Barr virus Early Antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the evaluated compounds, chlorpromazine, phenoxazine, ethylpropazine, 9-oxo-9H-thioxanthene-3-carbonitrile-10,10-dioxide, thiothixene and phenothiazine showed profound inhibition of EBV-EA in the in vitro assay. This activity was influenced by a modification of the phenothiazine ring. Replacement of nitrogen in the phenothiazine ring with sulfur atoms decreased the anti-tumor activity. Overall analysis showed that the simple tri-cyclic compound phenoxazine was the most active anti-tumor promoting compound in the test system. Therefore, we assessed the anti-tumor promoting effect of phenoxazine in vivo in two different chemical carcinogen-induced-promotion experimental models in mice namely the 7,12-dimethylbenz(a)anthracene (DMBA) initiated and TPA-promoted ICR mouse skin two-stage carcinogenesis protocol and the peroxynitrite (PN)-induced and TPA-promoted skin carcinogenesis in HOS:HR-1 mouse. Following tumor initiation with DMBA, topical application of 0.0025% phenoxazine to the dorsal initiated mouse skin resulted in a highly significant inhibition of TPA tumor promotion. The compound exhibited remarkable inhibitory effects on the mouse skin tumor promotion in terms of a reduction in tumor multiplicity (>50%) and incidence, accompanied by an extension of the tumor latency. In the PN-induced and TPA-promoted two-stage mouse skin carcinogenesis, oral administration of phenoxazine (0.0025%) for 2 weeks showed profound decrease in both the tumor incidence and burden by more than 20 and 80%, respectively, at 10 weeks of treatment. This was also accompanied by a 20% delay in the tumor latency period. In all the treatment groups, there was no toxicity due to phenoxazine in the treatment groups as compared to the control animals. These significant anti-tumor potentials of phenoxazine either via topical or oral administration might be due to the inherent cytotoxicity of these classes of compounds, which can be utilized in the prevention of development of overt tumors, immunopotentiation, induction of differentiation and apoptosis. In addition, since phenoxazine derivatives and other related phenothiazine compounds in use, as anti-psychotic agents without any reported adverse effect are known to pass the blood–brain barrier, they represent a new class of cancer chemopreventive agents with greater implication in the prevention of brain cancers.

Harukuni Tokuda - One of the best experts on this subject based on the ideXlab platform.

  • absolute configuration of dihydro β agarofuran sesquiterpenes from maytenus jelskii and their potential antitumor promoting effects
    Journal of Natural Products, 2016
    Co-Authors: Nayra R Perestelo, Ignacio A. Jiménez, Harukuni Tokuda, Eiichiro Ichiishi, Jesus T Vazquez, Isabel L. Bazzocchi
    Abstract:

    Chemoprevention of human cancer appears to be a feasible strategy for cancer control, especially when chemopreventive intervention is involved during Early stages of the carcinogenesis process. As a part of our ongoing research program into new chemopreventive agents, herein are reported the isolation, structural elucidation, and biological evaluation of 10 new (1–10) and three known (11–13) sesquiterpenes with a dihydro-β-agarofuran skeleton from the leaves of Maytenus jelskii Zahlbr. Their stereostructures have been elucidated by means of spectroscopic analysis, including 1D and 2D NMR techniques, ECD studies, and biogenetic considerations. The isolated metabolites and eight previously reported sesquiterpenes (14–21) were screened for their antitumor-promoting activity using a short-term in vitro assay for Epstein–Barr virus Early Antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Six compounds from this series (4, 5, 11, and 13–15) were found to exhibit higher efficacies...

  • acetophenones from acronychia pedunculata and their cancer chemopreventive activity
    Natural Product Communications, 2016
    Co-Authors: Mari Hosono, Tian Shung Wu, Harukuni Tokuda, Masataka Itoigawa
    Abstract:

    : From the roots of Acronychia pedunculata (L.) Miq. (Rutaceae) collected in Taiwan, six known and three new acetophenones have been isolated. The new compounds were named acrophenones D (1), E (2), and F (3). Of the acetophenones isolated in this study, prenylacronylin (4) and acronyculatin D. (10) exhibited significant inhibitory activity against 12-0-tetradecanoylphorbol 13-acetate-induced Epstein-Barr virus Early Antigen activation in Raji cells.

  • cytotoxic and melanogenesis inhibitory activities of limonoids from the leaves of azadirachta indica neem
    ChemInform, 2014
    Co-Authors: Mio Takagi, Harukuni Tokuda, Motohiko Ukiya, Norihiro Banno, Yosuke Tachi, Jie Zhang, Takuro Shinozaki, Kenta Ishii, Takashi Kikuchi, Toshihiro Akihisa
    Abstract:

    isolation, structure elucidation and evaluation of 17 limonoids, including the three novel ones (I), (II), (III), for their cytotoxic activities, their inhibitory activities against melanogenesis in B16 melanoma cells and against the Epstein—Barr virus Early Antigen

  • chemoprevention of skin cancer effect of lawsonia inermis l henna leaf powder and its pigment artifact lawsone in the epstein barr virus Early Antigen activation assay and in two stage mouse skin carcinogenesis models
    Anti-cancer Agents in Medicinal Chemistry, 2013
    Co-Authors: Govind J Kapadia, Akira Iida, Takao Konoshima, Nobutaka Suzuki, Subba G Rao, Rajagopalan Sridhar, Eiichiro Ichiishi, Midori Takasaki, Harukuni Tokuda
    Abstract:

    In continuation of our studies with chemoprevention potential of plant-derived naphthoquinone derivatives, leaf powder of the medicinal plant Lawsonia inermis L, commonly known as ‘henna’, was evaluated by its inhibition of the Epstein-Barr virus Early Antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Lawsone (2-hydroxy- 1,4-naphthoquinone), the reddish orange pigment artifact formed during the extraction or preparation of the dye from henna leaves and believed to be the active component, was also assessed in this in vitro assay. Both showed a profound inhibition (>88%) of EBV-EA activation. In the in vivo two-stage mouse skin carcinogenesis study using UV-B radiation for initiation and TPA for tumor promotion, oral feeding of henna (0.0025%) in drinking water ad libitum decreased tumor incidence by 66% and multiplicity by 40% when compared to the positive control at 10 weeks of treatment. Similarly, in the above mouse model, orally fed lawsone (0.0025%) decreased tumor incidence by 72% and multiplicity by 50%. The tumor inhibitory trend continued throughout the 20-week test period. Similar antitumor activities were observed when henna (0.5 mg/ml) was applied topically on the back skin in the UV-B initiated, TPA promoted and peroxynitrite initiated, TPA promoted mouse skin carcinogenesis models. Topically applied lawsone (0.015 mg/ml) also exhibited similar protection against tumor formation in the 7,12-dimtehylbenz(a)anthracene induced and TPA promoted skin cancer in mice. Also, there was a delay of 1 to 2 weeks in tumor appearance in both henna and lawsone treated groups compared to control in all three test models. This study ascertains the skin cancer chemopreventive activity of henna leaf powder and lawsone when administered by either oral (through drinking water) or topical (by application on the back skin) routes. Further, it emphasizes the need for the evaluation of these henna-derived green chemopreventive candidates in combination with currently used sunscreen agents for complementary anticancer potential against UV-induced skin carcinogenesis.

  • identification and biological activities of bryostatins from japanese bryozoan
    Bioscience Biotechnology and Biochemistry, 2012
    Co-Authors: Sayo Ueno, Ryo C Yanagita, Harukuni Tokuda, Akira Murakami, Nobutaka Suzuki, Takeshi Fujiwara, Kazuma Murakami, Kazuhiro Irie
    Abstract:

    Six bryostatins were isolated from Japanese bryozoan by evaluating their binding to the C1B domain of protein kinase Cδ (PKCδ). Structure-activity studies of bryostatins 4, 10, and 14 suggested that the ester group at C20 was not necessary for binding to and activating PKCδ. These bryostatins showed significant anti-tumor-promoting activity in induction tests with the Epstein-Barr virus Early Antigen.

Masataka Itoigawa - One of the best experts on this subject based on the ideXlab platform.

  • acetophenones from acronychia pedunculata and their cancer chemopreventive activity
    Natural Product Communications, 2016
    Co-Authors: Mari Hosono, Tian Shung Wu, Harukuni Tokuda, Masataka Itoigawa
    Abstract:

    : From the roots of Acronychia pedunculata (L.) Miq. (Rutaceae) collected in Taiwan, six known and three new acetophenones have been isolated. The new compounds were named acrophenones D (1), E (2), and F (3). Of the acetophenones isolated in this study, prenylacronylin (4) and acronyculatin D. (10) exhibited significant inhibitory activity against 12-0-tetradecanoylphorbol 13-acetate-induced Epstein-Barr virus Early Antigen activation in Raji cells.

  • cancer chemopreventive activity of terpenoid coumarins from ferula species
    Planta Medica, 2008
    Co-Authors: Mehrdad Iranshahi, Harukuni Tokuda, Hiroshi Furukawa, Chihiro Ito, Farhad Kalategi, Ramin Rezaee, Ahmad Reza Shahverdi, Masataka Itoigawa
    Abstract:

    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

  • cancer chemopreventive activity of rotenoids from derris trifoliata
    Planta Medica, 2004
    Co-Authors: Masataka Itoigawa, Junko Takayasu, Hoyoku Nishino, Naoki Kojima, Hiroshi Furukawa
    Abstract:

    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.

  • cancer chemopreventive activity of acridone alkaloids on epstein barr virus activation and two stage mouse skin carcinogenesis
    Cancer Letters, 2003
    Co-Authors: Fumio Enjo, Hoyoku Nishino, Masataka Itoigawa, Harukuni Tokuda, Chihiro Ito, Hiroshi Furukawa
    Abstract:

    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.

  • chemical constituents of calophyllum brasiliense 2 structure of three new coumarins and cancer chemopreventive activity of 4 substituted coumarins
    Journal of Natural Products, 2003
    Co-Authors: Chihiro Ito, Fumio Enjo, Hoyoku Nishino, Masataka Itoigawa, Harukuni Tokuda, Yoshitaka Mishina, Valdir Cechinel Filho, Hiroshi Furukawa
    Abstract:

    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.

Hiroshi Furukawa - One of the best experts on this subject based on the ideXlab platform.

  • cancer chemopreventive activity of terpenoid coumarins from ferula species
    Planta Medica, 2008
    Co-Authors: Mehrdad Iranshahi, Harukuni Tokuda, Hiroshi Furukawa, Chihiro Ito, Farhad Kalategi, Ramin Rezaee, Ahmad Reza Shahverdi, Masataka Itoigawa
    Abstract:

    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

  • cancer chemopreventive activity of rotenoids from derris trifoliata
    Planta Medica, 2004
    Co-Authors: Masataka Itoigawa, Junko Takayasu, Hoyoku Nishino, Naoki Kojima, Hiroshi Furukawa
    Abstract:

    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.

  • cancer chemopreventive activity of acridone alkaloids on epstein barr virus activation and two stage mouse skin carcinogenesis
    Cancer Letters, 2003
    Co-Authors: Fumio Enjo, Hoyoku Nishino, Masataka Itoigawa, Harukuni Tokuda, Chihiro Ito, Hiroshi Furukawa
    Abstract:

    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.

  • chemical constituents of calophyllum brasiliense 2 structure of three new coumarins and cancer chemopreventive activity of 4 substituted coumarins
    Journal of Natural Products, 2003
    Co-Authors: Chihiro Ito, Fumio Enjo, Hoyoku Nishino, Masataka Itoigawa, Harukuni Tokuda, Yoshitaka Mishina, Valdir Cechinel Filho, Hiroshi Furukawa
    Abstract:

    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.

  • chemical constituents of garcinia fusca structure elucidation of eight new xanthones and their cancer chemopreventive activity
    Journal of Natural Products, 2003
    Co-Authors: Masataka Itoigawa, Tomoko Takakura, Nijisiri Ruangrungsi, Fumio Enjo, Harukuni Tokuda, Hiroshi Furukawa
    Abstract:

    We describe the isolation and spectrometric structure elucidation of eight new xanthones, fuscaxanthone A (1), B (2), C (3), D (4), E (5), F (6), G (7), and H (8), together with eight known xanthones from the stem bark of Garcinia fusca collected in Thailand. All the new xanthones were shown to have a terpenoid (prenyl and/or geranyl) side chain(s) in their molecules. We also present the results of a primary screening of the inhibitory effects of eight xanthones (9−16) isolated as major components of this plant on 12-O-tetradecanoylphorbol-13-acetate induced Epstein−Barr virus Early Antigen activation in Raji cells.

Takao Konoshima - One of the best experts on this subject based on the ideXlab platform.

  • chemoprevention of skin cancer effect of lawsonia inermis l henna leaf powder and its pigment artifact lawsone in the epstein barr virus Early Antigen activation assay and in two stage mouse skin carcinogenesis models
    Anti-cancer Agents in Medicinal Chemistry, 2013
    Co-Authors: Govind J Kapadia, Akira Iida, Takao Konoshima, Nobutaka Suzuki, Subba G Rao, Rajagopalan Sridhar, Eiichiro Ichiishi, Midori Takasaki, Harukuni Tokuda
    Abstract:

    In continuation of our studies with chemoprevention potential of plant-derived naphthoquinone derivatives, leaf powder of the medicinal plant Lawsonia inermis L, commonly known as ‘henna’, was evaluated by its inhibition of the Epstein-Barr virus Early Antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Lawsone (2-hydroxy- 1,4-naphthoquinone), the reddish orange pigment artifact formed during the extraction or preparation of the dye from henna leaves and believed to be the active component, was also assessed in this in vitro assay. Both showed a profound inhibition (>88%) of EBV-EA activation. In the in vivo two-stage mouse skin carcinogenesis study using UV-B radiation for initiation and TPA for tumor promotion, oral feeding of henna (0.0025%) in drinking water ad libitum decreased tumor incidence by 66% and multiplicity by 40% when compared to the positive control at 10 weeks of treatment. Similarly, in the above mouse model, orally fed lawsone (0.0025%) decreased tumor incidence by 72% and multiplicity by 50%. The tumor inhibitory trend continued throughout the 20-week test period. Similar antitumor activities were observed when henna (0.5 mg/ml) was applied topically on the back skin in the UV-B initiated, TPA promoted and peroxynitrite initiated, TPA promoted mouse skin carcinogenesis models. Topically applied lawsone (0.015 mg/ml) also exhibited similar protection against tumor formation in the 7,12-dimtehylbenz(a)anthracene induced and TPA promoted skin cancer in mice. Also, there was a delay of 1 to 2 weeks in tumor appearance in both henna and lawsone treated groups compared to control in all three test models. This study ascertains the skin cancer chemopreventive activity of henna leaf powder and lawsone when administered by either oral (through drinking water) or topical (by application on the back skin) routes. Further, it emphasizes the need for the evaluation of these henna-derived green chemopreventive candidates in combination with currently used sunscreen agents for complementary anticancer potential against UV-induced skin carcinogenesis.

  • cancer preventive agents part 8 chemopreventive effects of stevioside and related compounds
    Bioorganic & Medicinal Chemistry, 2009
    Co-Authors: Midori Takasaki, Junko Takayasu, Hoyoku Nishino, Takao Konoshima, Harukuni Tokuda, Mutsuo Kozuka, Masazumi Miyakoshi, Kenji Mizutani
    Abstract:

    Abstract In a search for potential cancer chemopreventive agents from natural resources, stevioside ( 1 ), a sweetener, and six related compounds, including two aglycones steviol ( 6 ) and isosteviol ( 7 ), were screened in an in vitro assay for inhibitory effects on Epstein–Barr virus Early Antigen activation. Compounds 1 , 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[ a ]anthracene (DMBA) and 12- O -tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of these three compounds were greater than that of glycyrrhizin. Furthermore, these three compounds significantly inhibited mouse skin carcinogenesis initiated by peroxynitrite and promoted by TPA. Their activities were comparable to that of curcumin. These results suggested that 1 , as well as 6 and 7 , could be valuable as chemopreventive agents for chemical carcinogenesis.

  • cancer chemopreventive effect of phenothiazines and related tri heterocyclic analogues in the 12 o tetradecanoylphorbol 13 acetate promoted epstein barr virus Early Antigen activation and the mouse skin two stage carcinogenesis models
    Pharmacological Research, 2004
    Co-Authors: Magnus A Azuine, Junko Takayasu, Fumio Enjyo, Teruo Mukainaka, Hoyoku Nishino, Takao Konoshima, Harukuni Tokuda, Govind J Kapadia
    Abstract:

    Abstract In continuation of our search for novel agents, we have investigated 29 phenothiazines and related tri-heterocyclic compounds as potential cancer chemopreventive agents in a short-term in vitro assay of Epstein-Barr virus Early Antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the evaluated compounds, chlorpromazine, phenoxazine, ethylpropazine, 9-oxo-9H-thioxanthene-3-carbonitrile-10,10-dioxide, thiothixene and phenothiazine showed profound inhibition of EBV-EA in the in vitro assay. This activity was influenced by a modification of the phenothiazine ring. Replacement of nitrogen in the phenothiazine ring with sulfur atoms decreased the anti-tumor activity. Overall analysis showed that the simple tri-cyclic compound phenoxazine was the most active anti-tumor promoting compound in the test system. Therefore, we assessed the anti-tumor promoting effect of phenoxazine in vivo in two different chemical carcinogen-induced-promotion experimental models in mice namely the 7,12-dimethylbenz(a)anthracene (DMBA) initiated and TPA-promoted ICR mouse skin two-stage carcinogenesis protocol and the peroxynitrite (PN)-induced and TPA-promoted skin carcinogenesis in HOS:HR-1 mouse. Following tumor initiation with DMBA, topical application of 0.0025% phenoxazine to the dorsal initiated mouse skin resulted in a highly significant inhibition of TPA tumor promotion. The compound exhibited remarkable inhibitory effects on the mouse skin tumor promotion in terms of a reduction in tumor multiplicity (>50%) and incidence, accompanied by an extension of the tumor latency. In the PN-induced and TPA-promoted two-stage mouse skin carcinogenesis, oral administration of phenoxazine (0.0025%) for 2 weeks showed profound decrease in both the tumor incidence and burden by more than 20 and 80%, respectively, at 10 weeks of treatment. This was also accompanied by a 20% delay in the tumor latency period. In all the treatment groups, there was no toxicity due to phenoxazine in the treatment groups as compared to the control animals. These significant anti-tumor potentials of phenoxazine either via topical or oral administration might be due to the inherent cytotoxicity of these classes of compounds, which can be utilized in the prevention of development of overt tumors, immunopotentiation, induction of differentiation and apoptosis. In addition, since phenoxazine derivatives and other related phenothiazine compounds in use, as anti-psychotic agents without any reported adverse effect are known to pass the blood–brain barrier, they represent a new class of cancer chemopreventive agents with greater implication in the prevention of brain cancers.

  • anticarcinogenic activity of natural sweeteners cucurbitane glycosides from momordica grosvenori
    Cancer Letters, 2003
    Co-Authors: Midori Takasaki, Hoyoku Nishino, Takao Konoshima, Harukuni Tokuda, Yuji Murata, Masaki Sugiura, Kazuhiro Matsumoto, Ryoji Kasai, Kazuo Yamasaki
    Abstract:

    Abstract To search for cancer chemopreventive agents from natural resources, many phytochemicals and food additives have been screened. Consequently, two natural sweeteners, mogroside V and 11-oxo-mogroside V isolated from the fruits of Momordica grosvenori , exhibited strong inhibitory effect on the primary screening test indicated by the induction of Epstein-Barr virus Early Antigen (EBV-EA) by a tumor promoter, 12- O -tetradecanoylphorbol-13-acetate (TPA). These sweet glycosides, having cucurbitane triterpenoid aglycon, exhibited the significant inhibitory effects on the two-stage carcinogenesis test of mouse skin tumors induced by peroxynitrite (ONOO − ) as an initiator and TPA as a promoter. Further, 11-oxo-mogroside V also exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumor induced by 7,12-dimethylbenz[ a ]anthracene (DMBA) as an initiator and TPA as a promoter.

  • chemopreventive effect of resveratrol sesamol sesame oil and sunflower oil in the epstein barr virus Early Antigen activation assay and the mouse skin two stage carcinogenesis
    Pharmacological Research, 2002
    Co-Authors: Govind J Kapadia, Teruo Mukainaka, Takao Konoshima, Magnus A Azuine, Harukuni Tokuda, Midori Takasaki, Hoyoku Nishino
    Abstract:

    Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus Early Antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus Early Antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse skin tumor model. The anti-oxidant capabilities of these compounds could not solely explain the observed anti-cancer characteristics. Resveratrol is present in grapes. Sesamol, a constituent of sesame oil and sunflower oil are regularly consumed dietary natural products. The observed chemopreventive effect of these products particularly warrants more attention since they already exist in the population with no known adverse effects.