RESUMO
In our continuing search for novel cancer chemopreventive compounds of natural and synthetic origin, we have evaluated 14 commonly used ultraviolet (UV) sunscreen agents (designated UV-1 to UV-14) for their skin cancer chemoprevention potential. They belong to 8 different chemical categories: aminobenzoate (UV-5, UV-7, UV-8 and UV-14), benzophenone (UV-1, UV-2, UV-3 and UV-13), benzotriazole (UV-10), benzyloxyphenol (UV-9), cinnamate (UV-6), quinolone (UV-4), salicylate (UV-11) and xanthone (UV-12). In the in vitro assay employed, the sunscreens were assessed by their inhibition of the Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in human lymphoblastoid Raji cells. All sunscreens tested were found to exhibit anti-tumour promoting activity: listed in decreasing order, moderate (UV-11, UV-2, UV-7, UV-12, UV-3, UV-9 and UV-14) to weak (UV-1, UV-6, UV-8, UV-16, UV-5, UV-4 and UV-10) with octyl salicylate (UV-11) as the most potent and drometrizole (UV-10) as the least potent among the compounds evaluated. A plausible relationship between the antioxidant property of sunscreens and their ability to promote anti-tumour activity was noted. The results call for a comprehensive analysis of skin cancer chemoprevention potential of currently used UV sunscreen agents around the globe to identify those with the best clinical profile.
Assuntos
Antígenos Virais/imunologia , Neoplasias Cutâneas/prevenção & controle , Protetores Solares/uso terapêutico , Carcinógenos/toxicidade , Humanos , Técnicas In Vitro , Neoplasias Cutâneas/induzido quimicamente , Acetato de Tetradecanoilforbol/toxicidadeRESUMO
A prenylated coumarin (diversin, 1) together with four new sesquiterpene lactones (diversolides A, D, F and G, 2-5) isolated from the roots of Ferula diversivittata were studied for their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). All of the tested compounds were active against EBV-EA activation. Among these compounds diversin (IC(50): 7.7) exhibited the strongest inhibitory effect and was selected to examine its effects on in vivo two-stage mouse skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and TPA as promoter. Treatment with compound 1 (85nmol) along with DMBA/TPA inhibited papilloma formation up to week 7 and the percentage of papilloma bearers was approximately 93.3% at week 20. The average number of papillomas formed per mouse was only 5.5 even at week 20. The results of the present investigation indicated that diversin might be valuable as a potent cancer chemopreventive agent and its potency was comparable with those of curcumin and quercetin, two well-known cancer chemopreventive agents.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Cumarínicos/uso terapêutico , Ferula/química , Monoterpenos/uso terapêutico , Papiloma/prevenção & controle , Extratos Vegetais/uso terapêutico , Neoplasias Cutâneas/prevenção & controle , 9,10-Dimetil-1,2-benzantraceno , Animais , Antígenos Virais/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Carcinógenos , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Feminino , Lactonas/isolamento & purificação , Lactonas/farmacologia , Lactonas/uso terapêutico , Camundongos , Camundongos Endogâmicos ICR , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Papiloma/patologia , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Pele/efeitos dos fármacos , Pele/patologia , Neoplasias Cutâneas/patologia , Acetato de TetradecanoilforbolRESUMO
Oral administration of red ginseng extracts (1% in diet for 40 weeks) resulted in the significant suppression of spontaneous liver tumor formation in C3H/He male mice. Average number of tumors per mouse in control group was 1.06, while that in red ginseng extracts-treated group was 0.33 (p<0.05). Incidence of liver tumor development was also lower in red ginseng extracts-treated group, although the difference from control group was not statistically significant. Anti-carcinogenic activity of white ginseng extracts, besides red ginseng extracts, was also investigated. In the present study, the administration of white ginseng extracts was proven to suppress tumor promoter-induced phenomena in vitro and in vivo. It is of interest that oral administration of the extracts of Ren-Shen-Yang- Rong-Tang, a white ginseng-containing Chinese medicinal prescription, resulted in the suppression of skin tumor promotion by 12-o-tetradecanoylphorbol-13-acetate in 7,12-dimethylbenz[a]anthracene-initiated CD-1 mice. These results suggest the usefulness of ginseng in the field of cancer prevention.
Assuntos
Anticarcinógenos/farmacologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Panax , Neoplasias Cutâneas/prevenção & controle , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C3H , Extratos Vegetais/farmacologia , Raízes de PlantasRESUMO
To search for cancer chemopreventive agents from natural resources, many phytochemicals have been screened using the in vitro synergistic assay indicated by the inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA). Two phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, were isolated from the aerial part of Polygonum lapathifolium as inhibitors on the EBV-EA induction. These compounds also exhibited significant anti-tumor-promoting effects on mouse two-stage skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA, as an initiator) and TPA as a promoter. Further, vanicoside B exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors initiated with an NO donor, NOR-1.
Assuntos
Anticarcinógenos/farmacologia , Cinamatos/farmacologia , Dissacarídeos/farmacologia , Ésteres/química , Neoplasias/prevenção & controle , Animais , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos ICR , Modelos Químicos , Doadores de Óxido Nítrico/farmacologia , Sacarose/química , Acetato de Tetradecanoilforbol/metabolismo , Fatores de TempoRESUMO
Four new phenylpropanoid esters of sucrose, lapathosides A (1), B (2), C (3), and D (4), were isolated from the aerial parts of Polygonum lapathifolium together with known esters, vanicoside B (5) and hydropiperoside (6). The structures of 1-4 were determined by spectral (1D and 2D NMR and MS) analysis. Lapathoside A (1) and vanicoside B (2) showed significant inhibitory effects on the Epstein-Barr virus early antigen activation by tumor-promoters.
Assuntos
Anticarcinógenos/farmacologia , Antígenos Virais/efeitos dos fármacos , Cinamatos/isolamento & purificação , Dissacarídeos/isolamento & purificação , Antígenos Nucleares do Vírus Epstein-Barr/efeitos dos fármacos , Ésteres/química , Plantas Medicinais/química , Polygonum/química , Sacarose/análogos & derivados , Sacarose/química , Animais , Antígenos Virais/fisiologia , Cinamatos/química , Cinamatos/farmacologia , Dissacarídeos/química , Dissacarídeos/farmacologia , Relação Dose-Resposta a Droga , Antígenos Nucleares do Vírus Epstein-Barr/fisiologia , Humanos , Linfoma de Células B , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Medicina Tradicional Chinesa , Doadores de Óxido Nítrico/farmacologia , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Células Tumorais Cultivadas/efeitos dos fármacos , Ativação Viral/efeitos dos fármacosRESUMO
Two steroidal saponins, hemeroside A and B, were isolated from the aerial part of Hemerocallis fulva var. kwanso for the first time. The structures of these compounds were established as 24S-hydroxy-neotokorogenin 1-O-alpha-L-arabinopyranosyl 24-O-beta-D-glucopyranoside (1) and isorhodeasapogenin 3-O-beta-D-glucopyranosyl-(1-->3)-[beta-D-xylopyranosyl-(1-->2)]-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside (2) through NMR experiments.
Assuntos
Liliaceae/química , Plantas Medicinais/química , Saponinas/química , Saponinas/isolamento & purificação , Esteroides , Sequência de Carboidratos , Hidrólise , Espectroscopia de Ressonância Magnética , Conformação Molecular , Dados de Sequência Molecular , Extratos Vegetais/química , Espectrofotometria InfravermelhoRESUMO
Eight new diterpenoids (1-8) have been isolated from the wood of Excoecaria agallocha (Euphorbiaceae) and their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) in Raji cells were examined to search for potent anti-tumor-promoters from natural resources. Of these compounds, the secolabdane-type diterpenoid, compound 7 exhibited a remarkable inhibitory effect on EBV-EA induction, and a significant anti-tumor-promoting effect in the mouse two-stage carcinogenesis test using 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanovl-phorbol-13-acetate.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Diterpenos/uso terapêutico , Euphorbiaceae/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Transformação Celular Neoplásica/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Ensaios de Seleção de Medicamentos Antitumorais/estatística & dados numéricos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos ICR , Papiloma/tratamento farmacológico , Fitoterapia/métodos , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Células Tumorais CultivadasRESUMO
As part of our screening program for cancer inhibitory agents effective specifically in the promotion stage of cancer development, we have evaluated the possible inhibitory effects of 36 non-steroidal anti-inflammatory drugs (NSAIDs) on the Epstein-Barr virus early antigen (EBV-EA) activation which was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. All the drugs were observed to inhibit the EBV-EA activation at low doses with low toxicity. The two most active anti-tumor promoting agents were the arylacetic acid derivatives, etodolac and sulindac. We also report for the first time the activities of 14 new NSAIDs belonging to different classes as potential cancer chemopreventive agents. A structure-activity relationship study showed that among the salicylic acid derivative tested, the oxidation of the thiol group to dithiol derivatives results in the reduction of the activity. Introduction of amino group on the salicylic acid molecules also results in the reduction of activity in the EBV-EA assay. The results are of great interest in the development of NSAIDs as cancer chemopreventive agents, which halt cancer progression in multistage carcinogenesis, where successive activities are required to evolve into fully-fledged and metastatic cancer.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antígenos Virais/metabolismo , Carcinógenos , Neoplasias/prevenção & controle , Acetatos/farmacologia , Benzeno/farmacologia , Carcinoma/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Etodolac/farmacologia , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Neoplasias Nasofaríngeas/metabolismo , Oxirredução , Salicilatos/farmacologia , Relação Estrutura-Atividade , Sulindaco/farmacologia , Acetato de Tetradecanoilforbol , Células Tumorais CultivadasRESUMO
Eleven cyclic diarylheptanoids were screened as potential antitumor promoters by examining the ability of the compounds to inhibit Epstein-Barr virus early antigen activation (induced by 12-O-tetradecanoylphorbol-13-acetate) in Raji cells. 13-Oxomyricanol and myricanone showed the highest activity and also exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These data suggest that certain diarylheptanoids might be valuable antitumor promoters and/or chemopreventors.
Assuntos
Antineoplásicos/farmacologia , Diarileptanoides , Herpesvirus Humano 4/efeitos dos fármacos , Neoplasias Cutâneas/prevenção & controle , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Antineoplásicos/química , Carcinógenos/toxicidade , Relação Dose-Resposta a Droga , Feminino , Humanos , Hidrocarbonetos Cíclicos/química , Hidrocarbonetos Cíclicos/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Papiloma/induzido quimicamente , Papiloma/prevenção & controle , Neoplasias Cutâneas/induzido quimicamente , Organismos Livres de Patógenos Específicos , Terpenos/farmacologia , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo , Células Tumorais Cultivadas , Ativação Viral/efeitos dos fármacosRESUMO
A benzophenone glucoside and two flavonol glycosides were isolated together with 27 known polyphenols from the aerial parts of Coleogyne ramosissima, and their structures were elucidated by spectroscopic and chemical methods as iriflophenone 2-O-beta-glucopyranoside, isorhamnetin 3-O-2G-rhamnopyranosylrutinoside-7-O-alpha-rhamnopyranoside and limocitrin 3-O-rutinoside-7-O-beta-glucopyranoside, respectively.
Assuntos
Dissacarídeos/isolamento & purificação , Flavonoides/isolamento & purificação , Flavonóis , Glucosídeos/isolamento & purificação , Glicosídeos , Quercetina/análogos & derivados , Rosales/química , Trissacarídeos/isolamento & purificação , Configuração de Carboidratos , Dissacarídeos/química , Flavonoides/química , Glucosídeos/química , Espectroscopia de Ressonância Magnética , Análise Espectral , Trissacarídeos/químicaRESUMO
Ten sesquiterpenoids (1-10), with a dihydro-beta-agarofuran skeleton, were isolated from Maytenus cuzcoina (Celastraceae). Their structures were elucidated on the basis of spectral analysis, including homo- and heteronuclear correlations NMR experiments (COSY, ROESY, HMQC and HMBC), and chemical correlations. The compounds have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. Compounds 1-3, 6 and 7 showed strong inhibitory effects on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA). Their structure-activity relationship is discussed.
Assuntos
Sesquiterpenos/farmacologia , Antígenos Virais/efeitos dos fármacos , Antígenos Virais/metabolismo , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Plantas Medicinais/química , Sesquiterpenos/análise , Sesquiterpenos/isolamento & purificação , Espectrofotometria , Relação Estrutura-Atividade , Acetato de Tetradecanoilforbol/farmacologia , Células Tumorais CultivadasRESUMO
In the course of our continuing search for novel cancer chemopreventive agents from natural sources, several kinds of Compositae plants were screened. Consequently, the lignans, arctiin (ARC) and arctigenin (ARC-G), were obtained from the aerial part of Saussurea medusaas active constituents. These compounds exhibited the remarkable anti-tumor-promoting effect on two-stage carcinogenesis test of mouse skin tumors induced by 7, 12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoyl phorbol-13-acetate as a promoter by both topical application and oral administration. Furthermore, ARC-G exhibited potent anti-tumor-promoting activity on two-stage carcinogenesis test of mouse pulmonary tumors induced by 4-nitroquinoline-N-oxide as an initiator and glycerol as a promoter.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Asteraceae/química , Lignanas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fitoterapia , Neoplasias Cutâneas/tratamento farmacológico , 4-Nitroquinolina-1-Óxido , 9,10-Dimetil-1,2-benzantraceno , Administração Oral , Administração Tópica , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Glicerol , Neoplasias Pulmonares/induzido quimicamente , Camundongos , Camundongos Endogâmicos ICR , Camundongos Endogâmicos SENCAR , Transplante de Neoplasias , Neoplasias Cutâneas/induzido quimicamente , Acetato de TetradecanoilforbolRESUMO
In the course of our continuing search for novel cancer chemopreventive agents from natural sources, several kinds of Labiatae plants were screened. Consequently, the iridoid glycoside derivative, 8-acetylharpagide (8-AcHarp), was obtained from the flowering whole plant of Ajuga decumbens as an active constituent. This glycoside exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors induced by nitric oxide (NO) donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexen eamide (NOR 1) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter. Further, 8-AcHarp exhibited potent anti-tumor-promoting activity on two-stage carcinogenesis test of mouse hepatic tumor using N-nitrosodiethylamine (DEN) as an initiator and phenobarbital (PB) as a promoter.
Assuntos
Anticarcinógenos/uso terapêutico , Piranos/uso terapêutico , Animais , Anticarcinógenos/isolamento & purificação , Antígenos Virais/biossíntese , Carcinógenos , Dietilnitrosamina , Feminino , Glucosídeos/isolamento & purificação , Glucosídeos/uso terapêutico , Iridoides , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/prevenção & controle , Camundongos , Camundongos Endogâmicos ICR , Camundongos Endogâmicos SENCAR , Nitrocompostos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Piranos/isolamento & purificação , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/prevenção & controleRESUMO
In the course of our continuing search for novel cancer chemopreventive agents from natural sources, several kinds of Eucalyptus plants were screened. Consequently, the phlorogrucinol-monoterpene derivative, euglobal-G1 (EG-1), was obtained from the leaves of Eucalyptus grandis as an active constituent. EG-1 exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors induced by 7, 12-dimethylbenz[a]anthracene (DMBA) as an initiator and fumonisin-B1, which has been known as one of mycotoxins produced by Fusarium monifliforme, as a promoter. Further, EG-1 exhibited potent anti-tumor-promoting activity on two-stage carcinogenesis test of mouse pulmonary tumor using 4-nitroquinoline-N-oxide (4-NQO) as an initiator and glycerol as a promoter.
Assuntos
Anticarcinógenos/farmacologia , Eucalyptus/uso terapêutico , Fumonisinas , Neoplasias Pulmonares/prevenção & controle , Floroglucinol/análogos & derivados , Fitoterapia , Plantas Medicinais/uso terapêutico , Neoplasias Cutâneas/prevenção & controle , Terpenos/farmacologia , 4-Nitroquinolina-1-Óxido , 9,10-Dimetil-1,2-benzantraceno , Animais , Antivirais/farmacologia , Peso Corporal , Ácidos Carboxílicos , Carcinógenos , Carcinógenos Ambientais , Feminino , Glicerol , Neoplasias Pulmonares/induzido quimicamente , Camundongos , Camundongos Endogâmicos SENCAR , Neoplasias Experimentais/induzido quimicamente , Floroglucinol/química , Floroglucinol/farmacologia , Neoplasias Cutâneas/induzido quimicamente , Terpenos/química , Fatores de TempoRESUMO
Three novel diterpenoids, excoecarins D, E, and K (1-3), were isolated from Excoecaria agallocha. The structures of 1-3 were established as 3alpha,18-dihydroxy-3beta,20-epoxybeyer-15-ene, (15R, 16S)-ent-15,16-epoxybeyeran-3-one, and ent-3beta-hydroxykaur-16-en-2-one, respectively, on the basis of extensive NMR experiments and, in the case of 1, by X-ray analysis.
Assuntos
Diterpenos/isolamento & purificação , Euphorbiaceae/química , Diterpenos/química , Estrutura Molecular , Análise EspectralRESUMO
The extract of the roots of Panax notoginseng (Araliaceae) exhibited a significant anti-tumor-promoting activity on two-stage carcinogenesis of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and a mycotoxin, fumonisin B1, as a non-12-O-tetradecanoylphorbol-13-acetate (non-TPA) type promoter. Further, the extract exhibited the anti-tumor-initiating activity on two-stage carcinogenesis of mouse skin tumors induced by a nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexen amide (NOR-1) as an initiator and TPA as a promoter.
Assuntos
Anticarcinógenos/farmacologia , Panax/química , Papiloma/prevenção & controle , Plantas Medicinais , Neoplasias Cutâneas/prevenção & controle , 9,10-Dimetil-1,2-benzantraceno , Animais , Anticarcinógenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Camundongos , Papiloma/induzido quimicamente , Extratos Vegetais/uso terapêutico , Raízes de Plantas/química , Neoplasias Cutâneas/induzido quimicamenteRESUMO
Three series of monoacyl-2-O-beta-D-galactosylglycerols bearing an acyl chain of varying length, from C4 to C10, were studied due to their antitumor promoting effects on the activation of the Epstein-Barr virus early antigen (EBV-EA), such activation being induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This study indicates that it is more the length of the acyl chain that is important for the activity, six carbon atoms resulting in maximum effect, rather than the position of the ester function and the nature of the sugar (galactose or glucose).
Assuntos
Antineoplásicos/farmacologia , Glucosídeos/farmacologia , Herpesvirus Humano 4/efeitos dos fármacos , Ativação Viral/efeitos dos fármacos , Antígenos Virais/efeitos dos fármacos , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Glucosídeos/química , Herpesvirus Humano 4/crescimento & desenvolvimento , Humanos , Relação Estrutura-Atividade , Acetato de Tetradecanoilforbol/antagonistas & inibidores , Acetato de Tetradecanoilforbol/farmacologia , Células Tumorais CultivadasRESUMO
Chemical investigation on polyphenol-rich fractions of Cowania mexicana and Coleogyne ramosissima (Rosaceae) which showed significant inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), has led to the characterization of 10 compounds including C-glucosidic ellagitannin monomers and dimers from the former plant, and 17 polyphenols including flavonoid glycosides from the latter. The effects of individual components and their analogues with related structures on the TPA-induced EBV-EA activation were then evaluated. Among the compounds isolated from C. mexicana, two C-glucosidic ellagitannins, alienanin B and stenophyllanin A and a nitrile glucoside (lithospermoside), and among the constituents from C. ramosissima, two flavonoid glycosides, isorhamnetin 3-0-beta-D-glucoside and narcissin were revealed to possess strong inhibitory effects on EVB-EA activation, the potencies of which were either comparable to or stronger than that of a green tea polyphenol, (-)-epigallocatechin gallate. These polyphenols except for nitrile glucoside, which was not tested owing to an insufficient amount, were also found to exhibit anti-tumor promoting activity in two-stage mouse skin carcinogenesis using 7,12-dimethylbenz[a]anthracene (DMBA) and TPA.
Assuntos
Antineoplásicos/farmacologia , Flavonoides , Papiloma/tratamento farmacológico , Fenóis/farmacologia , Polímeros/farmacologia , Rosales/química , Neoplasias Cutâneas/tratamento farmacológico , Ativação Viral/efeitos dos fármacos , 9,10-Dimetil-1,2-benzantraceno , Animais , Antígenos Virais/efeitos dos fármacos , Antineoplásicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/crescimento & desenvolvimento , Humanos , Camundongos , Camundongos Endogâmicos ICR , Papiloma/induzido quimicamente , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Plantas Medicinais , Polímeros/isolamento & purificação , Polifenóis , Neoplasias Cutâneas/induzido quimicamente , Organismos Livres de Patógenos Específicos , Relação Estrutura-Atividade , Acetato de Tetradecanoilforbol , Células Tumorais CultivadasRESUMO
Sixteen compounds (1-16) isolated from the flowering whole plant of Ajuga decumbens have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) induction by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), as a primary screening test for antitumor-promoters (potential cancer chemopreventive agents). Five compounds (6, 9, and 12-14) showed strong inhibitory effects on EBV-EA induction. Of these active compounds, two major constituents of this plant, cyasterone (6) and 8-acetylharpagide (13), showed potent antitumor-promoting activities on a mouse-skin in vivo two-stage carcinogenesis procedure, using 7, 12-dimethylbenz[a]anthracene as initiator and TPA as promoter. Further, compound 13 also exhibited potent chemopreventive activity in a mouse pulmonary tumor model.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinógenos/antagonistas & inibidores , Plantas Medicinais/química , 4-Nitroquinolina-1-Óxido/toxicidade , Animais , Antivirais/farmacologia , Feminino , Glicerol/antagonistas & inibidores , Glicerol/toxicidade , Herpesvirus Humano 4/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/prevenção & controle , Camundongos , Camundongos Endogâmicos ICR , Papiloma/induzido quimicamente , Papiloma/prevenção & controle , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/prevenção & controle , Acetato de Tetradecanoilforbol/antagonistas & inibidores , Acetato de Tetradecanoilforbol/toxicidade , Células Tumorais CultivadasRESUMO
An extract of the roots of Taraxacum japonicum (Compositae) exhibited strong anti-tumor-promoting activities on the two-stage carcinogenesis of mouse skin tumor induced by dimethylbenz[a] anthracene (DMBA) as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter, as well as on that induced by DMBA and fumonisin B1. Further, the extract exhibited anti-tumor-initiating activity on the two-stage carcinogenesis of mouse skin tumor induced by (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexen amide (NOR-1) as an initiator and TPA as a promoter. These results suggested that an extract of the roots of the Taraxacum plant could be a valuable chemopreventive agent against chemical carcinogenesis.