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BACKGROUND: Many diseases may be caused by pathogens and oxidative stress resulting from carcinogens. Earlier studies have highlighted the antimicrobial and antioxidant effects of plant essential oils (EO). It is crucial to effectively utilize agricultural waste to achieve a sustainable agricultural economy and protect the environment. The present study aimed to evaluate the potential benefits of EO extracted from the discarded peels of Citrus depressa Hayata (CD) and Citrus microcarpa Bunge (CM), synonyms of Citrus deliciosa Ten and Citrus japonica Thunb, respectively. RESULTS: Gas chromatography-mass spectrometry analysis revealed that the main compounds in CD-EO were (R)-(+)-limonene (38.97%), γ-terpinene (24.39%) and linalool (6.22%), whereas, in CM-EO, the main compounds were (R)-(+)-limonene (48.00%), ß-pinene (13.60%) and γ-terpinene (12.07%). CD-EO exhibited inhibitory effects on the growth of common microorganisms, including Candida albicans, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. However, CM-EO showed only inhibitory effects on E. coli. Furthermore, CD-EO exhibited superior antioxidant potential, as demonstrated by its ability to eliminate 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis-3-ethylbenzthiazoline-6-sulfonate free radicals. Furthermore, CD-EO at a concentration of 100 µg mL-1 significantly inhibited 12-O-tetradecanoylphorbol-13-acetate-induced cancer transformation in mouse epidermal JB6 P+ cells (P < 0.05), possibly by up-regulating protein expression of nuclear factor erythroid 2-related factor 2 and its downstream antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase 1, heme oxygenase-1 and UGT1A. CONCLUSION: These findings suggest that CD-EO exhibits inhibitory effects on pathogenic microorganisms, possesses antioxidant properties and has cancer chemopreventive potential. © 2024 Society of Chemical Industry.
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Anti-Infecciosos , Citrus , Monoterpenos Cicloexânicos , Neoplasias , Óleos Voláteis , Animais , Camundongos , Óleos Voláteis/química , Antioxidantes/farmacologia , Antioxidantes/química , Limoneno/farmacologia , Citrus/química , Escherichia coli , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Óleos de Plantas/químicaRESUMO
Alkylating agents such as N-Ethyl-N-Nitrosourea (ENU) are ubiquitous within living cells and in the environment. This study designed to evaluate the chemopreventive activity of vanillic acid on ENU-induced toxicity and carcinogenesis in mice as an animal model of chronic lymphocytic leukemia (CLL). The female, Swiss albino mice were divided into three groups each with 7 mice, group I received normal saline, group II, mice received ENU at a dose of 80â¯mg/kg body weight i.p. to induce CLL on the 31th day of the study, and group III, the mice pretreated with vanillic acid at a dose of 20â¯mg/kg body weight/day, i.p. up to 30 days and received ENU. The animals were monitored for weight changes and mortality during 120 days, and then were sacrificed for isolation of lymphocytes, as target cells in CLL. Cellular parameters like reactive oxygen species (ROS) formation, malondialdehyde (MDA) production, depletion of glutathione (GSH), mitochondrial membrane potential (MMP) and lysosomal membrane integrity were studied. We found that pretreatment with vanillic acid significantly increased the survival of mice up to 57%, delay in death time (30%) and prevented weight changes after exposure to ENU. In addition, it was found that vanillic acid protected ROS formation, lipid peroxidation mitochondrial dysfunction, and lysosomal membrane destabilization in isolated lymphocytes. These data suggest that vanillic acid exhibited significant protection against ENU-induced toxicity and carcinogenicity, which might be related to the protection of the mitochondria and lysosomes and the reduction of ROS formation and oxidative stress.
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INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.
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Neoplasias da Mama , Quimioprevenção , Humanos , Feminino , Neoplasias da Mama/prevenção & controle , Quimioprevenção/métodos , Educação de Pacientes como Assunto/métodos , Técnicas de Apoio para a Decisão , Pessoa de Meia-Idade , Adulto , Tomada de Decisões , Conhecimentos, Atitudes e Prática em Saúde , Comportamento de Redução do Risco , Projetos de Pesquisa , Antagonistas de Estrogênios/uso terapêutico , Antagonistas de Estrogênios/administração & dosagem , Medidas de Resultados Relatados pelo PacienteRESUMO
Conventional treatments exhibit various side effects on chronic stress anemia. Extramedullary stress erythropoiesis is a compensatory mechanism, which may effectively counteract anemia. Angelica sinensis polysaccharides (ASP) are the main active ingredient found in Angelica sinensis and exhibit antioxidant and hematopoietic effects. However, the effects of ASP on extramedullary stress erythropoiesis remain to be unclear. Here, we demonstrated the protective effects of ASP on chemotherapeutic drug 5-fluorouracil (5-FU)-induced decline in peripheral blood parameters such as RBC counts, HGB, HCT, and MCH, and the decline of BFU-E colony enumeration in the bone marrow. Meanwhile, ASP promoted extramedullary erythropoiesis, increasing cellular proliferation in the splenic red pulp and cyclin D1 protein expression, abrogating phase G0/G1 arrest of c-kit+ cells in mouse spleen. RT-qPCR and immunohistochemistry further revealed that ASP increased macrophage chemokine Ccl2 genetic expression and the number of F4/80+ macrophages in the spleen. The colony-forming assay showed that ASP significantly increased splenic BFU-E. Furthermore, we found that ASP facilitated glycolytic genes including Hk2, Pgk1, Pkm, Pdk1, and Ldha via PI3K/Akt/HIF2α signaling in the spleen. Subsequently, ASP declined pro-proinflammatory factor IL-1ß, whereas upregulating erythroid proliferation-associated genes Gdf15, Bmp4, Wnt2b, and Wnt8a. Moreover, ASP facilitated EPO/STAT5 signaling in splenic macrophages, thus enhancing erythroid lineage Gata2 genetic expression. Our study indicated that ASP may improve glycolysis, promoting the activity of splenic macrophages, subsequently promoting erythroid progenitor cell expansion. Additionally, ASP facilitates erythroid differentiation via macrophage-mediated EpoR/STAT5 signaling; suggesting it might be a promising strategy for stress anemia treatment.
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Humans are frequently exposed to various carcinogens capable of inducing cancer in multiple organs. Phyllanthus emblica (P. emblica) is known for its strong antioxidant properties and potential in cancer prevention. However, its effectiveness against combined carcinogens remains relatively unexplored. This study aimed to assess the chemopreventive potential of the ethanolic extract of P. emblica fruits against preneoplastic lesions in the liver and colon using a rat model. Rats were administered with diethylnitrosamine (DEN) and 1,2-dimethylhydrazine (DMH) to induce hepato- and colon carcinogenesis, respectively. The ethanolic extract of P. emblica fruit at 100 and 500 mg/kg bw significantly reduced the number of preneoplastic lesions in the liver by 74.7% and 55.6%, respectively, and in the colon by 39.2% and 40.8%, respectively. Similarly, the extract decreased the size of preneoplastic lesions in the liver by 75.2% (100 mg/kg bw) and 70.6% (500 mg/kg bw). Furthermore, the extract significantly reduced the cell proliferation marker in the liver by 70.3% (100 mg/kg bw) and 61.54% (500 mg/kg bw), and in the colon by 62.7% (100 mg/kg bw) and 60.5% (500 mg/kg bw). The ethanolic extract also enhanced liver antioxidant enzyme activities and demonstrated free radical scavenging in DPPH, ABTS, and FRAP assays. Additionally, the dichloromethane fraction of P. emblica showed significant cancer prevention potential by reducing intracellular ROS and NO production by 61.7% and 35.4%, respectively, in RAW 264.7 macrophages. It also exhibited antimutagenic effects with a reduction of 54.0% against aflatoxin B1 and 52.3% against 2-amino-3,4-dimethylimidazo[4,5-f]quinoline-induced mutagenesis in Salmonella typhimurium. Finally, this study highlights the chemopreventive activity of P. emblica fruit extract against the initiation of early-stage carcinogenic lesions in the liver and colon in rats treated with dual carcinogens.
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Background/purpose: 4-Nitroquinoline 1-oxide (4NQO)-induced tongue carcinoma and 7,12-dimethlybenz(a)anthracene (DMBA)-induced cheek pouch carcinoma are the most common and classical chemical carcinogen-induced animal models of oral carcinogenesis. The purpose of this study was to provide the research trends and characteristics of 4NQO- and DMBA-induced experimental oral carcinogenesis. Materials and methods: The papers on both 4NQO- and DMBA-induced experimental oral carcinogenesis were published since 1962. All the eligible papers were retrieved on 12 May 2023 from the Scopus database. Results: There were 506 and 349 papers on 4NQO- and DMBA-induced experimental oral carcinogenesis with 10,152 and 6306 citations, respectively. The common distinctive keywords such as rat, tongue neoplasms, drinking water, tumor microenvironment, and cyclooxygenase (COX)-2 were identified in the papers on 4NQO; and the common keywords such as hamster, cheek pouch, lipid peroxidation, glutathione, antioxidants, and topical drug administration were identified in the papers on DMBA. Importantly, 105 and 65 potential chemopreventive agents were identified from the papers on 4NQO and DMBA, respectively. Furthermore, 15 promising agents such as COX-2 inhibitor, curcumin, garlic were researched concurrently in both the two animal models. Conclusion: This study for the first time reports the scientometric characteristics of 4NQO- and DMBA-induced experimental oral carcinogenesis. Importantly, we identify a valuable profile for oral cancer chemopreventive agents, which will aid researchers and investigators in studying oral cancer chemoprevention.
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The retinoid fenretinide (FENR) is a promising compound for preventing breast cancer recurrence but faces challenges due to poor solubility and low bioavailability. This study explores the development of dissolving microneedles (MNs) containing FENR-loaded ethosomes for minimally invasive breast cancer chemoprevention, aiming to enhance local drug distribution. Ethosomes were formulated using ethanol, propylene glycol, soya lecithin, water, and polysorbate 80 micelles. MNs were created from poly(vinyl alcohol) and poly(vinylpyrrolidone) hydrogels by adding polymer powder directly into ethosomes suspensions, reducing manufacturing time and cost. Two methods were used to load ethosomes into high-density moulds: 1) only in the needle area, and 2) in both the needle area and baseplate. Dynamic light scattering confirmed nanostructures in the hydrogels and MNs. Micelle-based ethosomes dissolved MNs in 15 min, compared to 30 min for other MNs. Skin deposition studies showed greater drug deposition (up to 10 µg/patch) and enhanced skin permeation of FENR (up to 40 µg) with Method 2. In-vivo studies in rats demonstrated that oral administration resulted in plasma FENR levels below 10 ng/g in the first three hours, whereas MN administration delayed delivery, reaching a maximum plasma concentration of 52 ng/g at 48 h. Skin deposition of FENR from MNs decreased from 3 µg/g on day 1 to <0.3 µg/g by the last day. This study indicates that MNs are a potential minimally invasive dosage form for delivering FENR, offering a new approach for breast cancer chemoprevention.
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Malignant tumors have increased energy requirements due to growth, differentiation or response to stress. A significant number of studies in recent years have described upregulation of mitochondrial genes responsible for oxidative phosphorylation (OXPHOS) in some tumors. Although OXPHOS is replaced by glycolysis in some tumors (Warburg effect), both processes can occur simultaneously during the evolution of the same malignancies. In particular, chemoresistant and/or cancer stem cells appear to find a way to activate OXPHOS and metastasize. In this paper, we discuss recent work showing upregulation of OXPHOS in chemoresistant tumors and cell models. In addition, we show an inverse correlation of OXPHOS gene expression with the survival time of cancer patients after chemotherapy and discuss combination therapies for resistant tumors.
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Neoplasias , Fosforilação Oxidativa , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , GlicóliseRESUMO
Research on retinoid-based cancer prevention, spurred by the effects of vitamin A deficiency on gastric cancer and subsequent clinical studies on digestive tract cancer, unveils novel avenues for chemoprevention. Acyclic retinoids like 4,5-didehydrogeranylgeranoic acid (4,5-didehydroGGA) have emerged as potent agents against hepatocellular carcinoma (HCC), distinct from natural retinoids such as all-trans retinoic acid (ATRA). Mechanistic studies reveal GGA's unique induction of pyroptosis, a rapid cell death pathway, in HCC cells. GGA triggers mitochondrial superoxide hyperproduction and ER stress responses through Toll-like receptor 4 (TLR4) signaling and modulates autophagy, ultimately activating pyroptotic cell death in HCC cells. Unlike ATRA-induced apoptosis, GGA and palmitic acid (PA) induce pyroptosis, underscoring their distinct mechanisms. While all three fatty acids evoke mitochondrial dysfunction and ER stress responses, GGA and PA inhibit autophagy, leading to incomplete autophagic responses and pyroptosis, whereas ATRA promotes autophagic flux. In vivo experiments demonstrate GGA's potential as an anti-oncometabolite, inducing cell death selectively in tumor cells and thus suppressing liver cancer development. This review provides a comprehensive overview of the molecular mechanisms underlying GGA's anti-HCC effects and underscores its promising role in cancer prevention, highlighting its importance in HCC prevention.
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Carcinoma Hepatocelular , Diterpenos , Neoplasias Hepáticas , Ácido Palmítico , Piroptose , Tretinoína , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Diterpenos/farmacologia , Ácido Palmítico/farmacologia , Piroptose/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Tretinoína/farmacologia , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático/efeitos dos fármacosRESUMO
2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) is a major compound in Cleistocalyx nervosum seed extract (CSE), which has been reported to have various biological activities, including anti-cancer activity. Therefore, this study attempted to evaluate whether DMC is a chemopreventive compound in CSE. Moreover, the preventive mechanisms of CSE and DMC in the DEN-induced early stages of hepatocarcinogenesis in rats were investigated. Male Wistar rats were intraperitoneally injected with DEN 50 mg/kg bw once a week for 8 weeks. Rats received CSE and DMC orally throughout the experiment. The number of glutathione S-transferase placental form (GST-P)-positive foci in the liver was measured. Furthermore, the preventive mechanisms of CSE and DMC on DEN-induced HCC, including cell proliferation and apoptosis, were investigated. Administering CSE at a dosage of 400 mg/kg bw and DMC at a dosage of 10 mg/kg bw significantly decreased the number and size of GST-P-positive foci and GST-P expression. In addition, DMC inhibited the development of preneoplastic lesions by decreasing cell proliferation and causing cell apoptosis; however, CSE inhibited the development of preneoplastic lesions by inducing cell apoptosis. In conclusion, DMC exhibited a cancer chemopreventive effect on the early stages of hepatocarcinogenesis by increasing cell apoptosis and reducing cell proliferation.
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Silymarin from milk thistle (Silybum marianum) has been reported to show an anti-cancer activity. In previous study, we reported that silymarin induces cyclin D1 proteasomal degradation through NF-κB-mediated threonine-286 phosphorylation. However, mechanism for the inhibition of Wnt signaling by silymarin still remains unanswered. Thus, we investigated whether silymarin affects Wnt signaling in human colorectal cancer cells to elucidate the additional anti-cancer mechanism of silymarin. Transient transfection with a TOP and FOP FLASH luciferase construct indicated that silymarin suppressed the transcriptional activity of β-catenin/TCF. Silymarin treatment resulted in a decrease of intracellular β-catenin protein but not mRNA. The inhibition of proteasome by MG132 and GSK3β inhibition by SB216763 blocked silymarin-mediated downregulation of β-catenin. In addition, silymarin increased phosphorylation of β-catenin and a point mutation of S33Y attenuated silymarin-mediated β-catenin downregulation. In addition, silymarin decreased TCF4 and increased Axin expression in both protein and mRNA level. From these results, we suggest that silymarin-mediated downregulation of β-catenin and TCF4 may result in the inhibition of Wnt signaling in human colorectal cancer cells.
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Humanos , Neoplasias Colorretais , Ciclina D1 , Regulação para Baixo , Luciferases , Silybum marianum , Fosforilação , Mutação Puntual , Complexo de Endopeptidases do Proteassoma , RNA Mensageiro , Silimarina , TransfecçãoRESUMO
Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. Activating transcription factor 3 (ATF3) is associated with apoptosis in human colon cancer cells. This study was performed to investigate the molecular mechanism by which NAR stimulates ATF3 expression and apoptosis in human colon cancer cells. NAR reduced the cell viability and induced an apoptosis in human colon cancer cells. ATF3 overexpression increased NAR-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by NAR. NAR increased ATF3 expression in both protein and mRNA level, and increased the luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by NAR is located between -317 and -148 of ATF3 promoter. p38 inhibition blocked NAR-mediated ATF3 expression, its promoter activation and apoptosis. The results suggest that NAR induces apoptosis through p38-dependent ATF3 activation in human colon cancer cells.
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Humanos , Fator 3 Ativador da Transcrição , Apoptose , Sobrevivência Celular , Citrus paradisi , Colo , Neoplasias do Colo , Flavonoides , Luciferases , RNA Mensageiro , Ativação TranscricionalRESUMO
The ginseng family, including Panax ginseng (Asian ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (notoginseng), is commonly used herbal medicine. White ginseng is prepared by air-drying after harvest, while red ginseng is prepared by a steaming or heating process. The anticancer activity of red ginseng is significantly increased, due to the production of active anticancer ginsenosides during the steaming treatment, compared with that of white ginseng. Thus far, anticancer studies have been mostly focused on Asian ginseng. In this article, we review the research progress made in the anticancer activities of red Asian ginseng, red American ginseng and red notoginseng. The major anticancer mechanisms of red ginseng compounds include cell cycle arrest, induction of apoptosis/paraptosis, and inhibition of angiogenesis. The structure-function relationship analysis has revealed that the protopanaxadiol group ginsenosides have more potent effects than the protopanaxatriol group. Sugar molecules in ginsenosides inversely impact the antiproliferative potential of these compounds. In addition, ginsenoside stereoselectivity and double bond position also influence the anticancer activity. Future studies should focus on characterizing active red ginseng derivatives as potential anticancer drugs.
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Animais , Humanos , Inibidores da Angiogênese , Farmacologia , Antineoplásicos Fitogênicos , Farmacologia , Apoptose , Ginsenosídeos , Farmacologia , Neoplasias , Tratamento Farmacológico , Panax , Química , Panax notoginseng , Química , Fitoterapia , Relação Estrutura-AtividadeRESUMO
Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells.
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Humanos , Alanina , Linhagem Celular , Proliferação de Células , Citrus paradisi , Neoplasias Colorretais , Ciclina D1 , Regulação para Baixo , Flavonoides , Meia-Vida , Fosforilação , Mutação PuntualRESUMO
Hot water extract of adlay (<i>Coix lachryma-jobi</i> L. <i>var. ma-yuen</i> Stapf) seed, commonly called Yokuinin, has been used as herbal medicine for treating verruca vulgaris, et al. Although there have been a number of studies on the usefulness of Yokuinin, the pharmacological assessment of its husk, pellicle, and astringent skin remains unclear. In this line, we evaluated the effect of methanol extract from all parts of adlay grain (seed, husk, pellicle, astringent skin) on cancer cells and identified its useful chemical components. Results revealed that a fraction of the extract have weak growth-suppressing activity on human cervical cancer cell line (HeLa cell). In particular, 5,7-dihydroxychromone and coixol were isolated and identified from the active fraction. This indicates the possible cancer chemopreventive efficacy of methanol extract from adlay. Moreover, further tests are needed to determine the role of 5,7-dihydroxychromone.<br>
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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.
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Feminino , Masculino , Camundongos , Animais , Anticarcinógenos/farmacologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Camundongos Endogâmicos C3H , Panax , Extratos Vegetais/farmacologia , Raízes de Plantas , Neoplasias Cutâneas/prevenção & controleRESUMO
Chemoprevention is currently regarded as one of the most promising avenues of cancer control. In the search for chemopreventive dietary plants and phytochemicals, the author has explored anti-tumor promotimg phytochemicals of vegetables and fruits in several Asian countries, using an inhibition test of tumor promoter-induced Epstein-Barr virus (EBV) activation. Extensive <i>in vitro</i> screening tests have found several dietary plants from subtropical zones to possess high potential. In particular, plants in families commonly ingested for purposes other than their nutritive value (<i>i.e.</i> as flavors, condiments, and occasionally traditional medicines) were shown to contain potent anti-tumor promoters. Of more than 50 <i>in vitro</i> anti-tumor promoters identified thus far, cancer preventive properties of 4 compounds from zingiberaceous (1′-acetoxychavicol acetate and zerumbone) and rutaceous (auraptene and nobiletin) plants have been further studied. The results of animal model experiments as well as modes of action, including anti-inflammation associated activities, are described. The present status of chemoprevention with food phytochemicals is also discussed.<br>
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Cancer chemoprevention utilizing food components is attracted because of its easily availability in humans. Bitter melon (<i>Momordica charantia</i>) (BMO) and pomegranate (<i>Punica granatum</i> L.) (PGO) seed oils contain a large amount of conjugated linolenic acid (CLN). In the first we demonstrated that BMO inhibits the development of azoxymethane (AOM)-induced putative precursor lesions for colonic adenocarcinoma in rats. Subsequently, we investigated the modifying effects of dietary administration of BMO or PGO on the development of colonic neoplasms using an animal colon carcinogenesis model initiated with a colon carcinogen AOM. Male F344 rats were given two weekly subcutaneous injections of AOM (20 mg/kg body weight) to induce colonic neoplasms. They were fed with the diets containing 0.01%, 0.1% and 1% BMO or PGO during the entire experimental period (for 32 weeks), starting one week before the first dosing of AOM. At the end of the study, the incidence and multiplicity of colonic adenocarcinoma were reduced in the "AOM+BMO" and "AOM+PGO" groups, when compared with the "gAOM alone" group. The contents of conjugated linoleic acid (CLA: 9<i>c</i>,11<i>t</i>-18:2) in the liver and colonic mucosa of rats fed BMO or PGO were elevated in a dose-dependent manner. Also, dietary BMO or PGO enhanced expression of peroxisome proliferator-activated receptor (PPAR)γ protein in the colonic mucosa. These findings may suggest that BMO or PGO rich in CLN can suppress AOM-induced colon carcinogenesis through the modification of lipid composition in the colon and liver and/or increased expression of PPARγ protein level in the colon mucosa. Our results might provide scientific evidence of an effective dietary chemopreventive approach using BMO and PGO seed oils rich in CLN to cancer chemoprevention, especially colon cancer development.<br>