Chemopreventive effect of chitosan oligosaccharide against colon carcinogenesis

Chitosan oligosaccharide (COS, 3 kDa相似文献   

Chemopreventive action of Phyllanthus urinaria Linn on DMBA-induced skin carcinogenesis in mice

The inhibition of tumor incidence by hydro-alcoholic extract of the whole plant of P. urinaria was evaluated in 6-7 weeks old female albino mice on two-stage process of skin carcinogenesis induced by a single application of 7,12-dimethylbenz(a)anthracene (50 microg/50 microl of acetone), and 2 weeks later, promoted by repeated application of croton oil (1% in acetone/three times a week) till the end of the experiment (15 weeks). Topical application of the extract at a dose of 5 mg/kg body weight/day for 15 weeks at the peri-initiational stage (i.e., 7 days before and 7 days after DMBA application), promotional stage (i.e., from the time of croton oil application) and both peri and post-initiational stages (i.e., 7 days prior to DMBA application and continued till the end of the experiment) on the shaven backs of the mice recorded a significant reduction in tumor incidence to 50, 33.3 and 16.7% respectively in comparison to the control (i.e., the mice treated with DMBA and croton oil only) where tumor incidence was found to be 81.8%. The average number of papillomas per mouse was also significantly reduced. The results suggest a possible chemopreventive property of P. urinaria against DMBA-induced skin papillomagenesis in mice.     

Antioxidants and multistage carcinogenesis in mouse skin

The two-step initiation-promotion protocol for the induction of skin tumors in mice is a convenient model to elucidate what molecular events are involved in the multistage process of carcinogenesis and how they can be modulated. The current theories concerning the mechanisms of skin tumor initiation, stages 1 and 2 of tumor promotion, and tumor progression are reviewed. Because chemical carcinogens and tumor promoters may, directly or indirectly, generate reactive oxygen species (ROS) and because various antioxidants inhibit effectively some of the biochemical and biological events linked to tumor initiation, promotion and/or progression, it is conceivable that different sequences and levels of free radical-induced macromolecule damage may contribute to the evolution of the epidermal target cells from the preneoplastic stage to the malignant stage.     

Chemopreventive effects of curcumin on chemically induced mouse skin carcinogenesis in BK5.insulin-like growth factor-1 transgenic mice

The insulin-like growth factor-1 (IGF-1) signaling pathway is strongly associated with the risk of various cancers, and its inhibition has emerged as a potent anticancer strategy. Accumulating evidence from in vitro studies has shown that curcumin is a potent inhibitor of the IGF-1 signaling pathway. However, direct evidence that curcumin modulates IGF-1-induced tumorigenesis in a physiological system has not been reported. Therefore, in this study, we assessed the anticarcinogenic activity of curcumin on skin cancer by using BK5.IGF-1 transgenic (Tg) mice that overexpress IGF-1 in the skin epidermis. In 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two-stage skin carcinogenesis, a curcumin diet (0.02% wt/wt) fed for 14 wk remarkably reduced mouse skin tumor multiplicity by 53%, epidermal hyperplasia and proliferation compared to the control diet group. TPA-induced phosphorylation of Akt, S6 kinase (S6K), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) in mouse skin was lower in the curcumin group than in the control group. Curcumin treatment inhibited IGF-1-induced phosphorylation of the IGF-1 receptor, insulin receptor substrate-1, Akt, S6K, and 4EBP1 in the mouse keratinocyte cell line, C50 in a dose-dependent manner. Taken together, these data suggest that curcumin exerts significant anticarcinogenic activity in skin cancer through the inhibition of IGF-1 signaling.     

Chemopreventive activities of Trigonella foenum graecum (Fenugreek) against breast cancer

Cancer is the second leading cause of death worldwide. Conventional therapies cause serious side effects and, at best, merely extend the patient's lifespan by a few years. Cancer control may therefore benefit from the potential that resides in alternative therapies. There is thus an increasing demand to utilize alternative concepts or approaches to the prevention of cancer. In this report, we show a potential protective effect of Fenugreek seeds against 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced breast cancer in rats. At 200 mg/kg b.wt., Fenugreek seeds' extract significantly inhibited the DMBA-induced mammary hyperplasia and decreased its incidence. Epidemiological studies also implicate apoptosis as a mechanism that might mediate the Fenugreek's anti-breast cancer protective effects. To our knowledge, this is the first study that suggests significant chemopreventive effects of Fenugreek seeds against breast cancer.     

Biological and molecular aspects of radiation carcinogenesis in mouse skin

The process of mouse skin carcinogenesis can be operationally subdivided into at least three stages which have been termed initiation, promotion, and progression. Ionizing radiation has been found to be a weak initiator of malignant squamous cell carcinomas (SCCs) when radiation was followed by repeated treatments of the skin with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Besides SCCs, ionizing radiation was found to induce, independent of tumor promoters, basal cell carcinomas (BCCs), a tumor histology not normally seen with chemical carcinogens and mouse skin. Fractionated doses of 1 MeV electrons were found to enhance the conversion of chemically induced benign papillomas to malignant SCCs. In addition to the biological studies, questions related to dominant transforming genes and differential gene expression in the radiation-initiated mouse skin tumors have been explored. Distinct non-ras dominant transforming gene(s) have been detected in radiation-initiated, TPA-promoted SCCs. Differences in the expression pattern of tumor-associated genes were seen in comparing chemically to radiation-induced benign and malignant skin tumors. Therefore, ionizing radiation has been shown to be active in the initiation of malignant skin tumors and progression of benign to malignant tumors in the mouse skin. The ability to divide the process of carcinogenesis into multiple stages in the mouse skin model has facilitated mechanistic studies that may elucidate the molecular pathways involved in radiation-versus chemically induced tumor development.     

Chemopreventive efficacy of geraniol against 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

The status of lipid peroxidation, antioxidants, and detoxification enzymes were used as biochemical end points to assess the chemopreventive potential of geraniol, a monoterpene, in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA in liquid paraffin, three times a week, for 14 weeks developed well-differentiated squamous cell carcinoma in the buccal pouch of golden Syrian hamsters. Although 100% tumor formation was noticed in hamsters treated with DMBA alone, intragastric administration of geraniol, at a dose of 250 mg/kg body weight (b.w.) to DMBA-treated hamster completely prevented the formation of oral tumors. Furthermore, geraniol significantly reduced lipid peroxidation by-products and improved the status of enzymatic and non-enzymatic antioxidants as well as modulated the status of phase I and phase II detoxification enzymes, favoring the excretion of carcinogenic metabolite, during DMBA-induced oral carcinogenesis. The present study concludes that the chemopreventive potential of geraniol relies on its anti-lipid peroxidative and antioxidant function as well as modulatory effects on phase I and II detoxification enzymes to excrete the carcinogenic metabolite, during DMBA-induced hamster buccal pouch carcinogenesis.     

Chemopreventive efficacy of geraniol against 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

Abstract

The status of lipid peroxidation, antioxidants, and detoxification enzymes were used as biochemical end points to assess the chemopreventive potential of geraniol, a monoterpene, in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA in liquid paraffin, three times a week, for 14 weeks developed well-differentiated squamous cell carcinoma in the buccal pouch of golden Syrian hamsters. Although 100% tumor formation was noticed in hamsters treated with DMBA alone, intragastric administration of geraniol, at a dose of 250 mg/kg body weight (b.w.) to DMBA-treated hamster completely prevented the formation of oral tumors. Furthermore, geraniol significantly reduced lipid peroxidation by-products and improved the status of enzymatic and non-enzymatic antioxidants as well as modulated the status of phase I and phase II detoxification enzymes, favoring the excretion of carcinogenic metabolite, during DMBA-induced oral carcinogenesis. The present study concludes that the chemopreventive potential of geraniol relies on its anti-lipid peroxidative and antioxidant function as well as modulatory effects on phase I and II detoxification enzymes to excrete the carcinogenic metabolite, during DMBA-induced hamster buccal pouch carcinogenesis.     

Evidence for and possible mechanisms of non-genotoxic carcinogenesis in mouse skin

Most chemicals that produce skin cancer are genotoxic by in vitro and in vivo short-term assays and produce a high incidence of skin cancer within a year if optimal doses are applied. If in long-term skin painting studies one or two tumours in 50 mice are observed there is a general consensus that no carcinogenic activity can be claimed and it has been suggested that if up to 10% tumours are induced by irritant substances this could be due to an enhancement of spontaneous tumour incidence. Observations of skin tumour incidences higher than 10% with non-genotoxic substances, usually after a long latent period, is considered to represent evidence for a non-genotoxic mechanism. Examples of such substances include croton oil, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), sodium hydroxide, potassium hydroxide, phenol, dodecylbenzene and petroleum-derived middle distillates. Two distinct mechanisms appear to be involved in the production of tumours by a non-genotoxic substance. The first of these is that seen with the strong promoting agents. These, by binding to and activating protein kinase C, appear to directly stimulate sustained epidermal hyperplasia without severe skin damage. The other appears to involve substances producing severe skin damage either by a direct caustic effect or by cumulative irritancy. These changes give rise to marked epidermal hyperplasia with repeated episodes of regeneration and damage. The tumour induction by both mechanisms probably results from oncogene activation and it is possible that oxidative enzymes from inflammatory cells may be involved in the activation process. Various reasons are given why non-genotoxic carcinogenesis in the skin is considered not to be relevant to man and ways of recognising and avoiding its occurrence in animals studies are recommended.     

Chemopreventive efficacy of betel leaf extract and its constituents on 7,12-dimethylbenz(a)anthracene induced carcinogenesis and their effect on drug detoxification system in mouse skin

Effects of topically applied betel leaf extract (BLE) and its constituents. beta-carotene, alpha-tocopherol, eugenol and hydroxychavicol on 7,12-dimethylbenz(a)anthracene (DMBA) induced skin tumors were evaluated in two strains of mice. BLE, beta-carotene and alpha-tocopherol, significantly inhibited the tumor formation by 83, 86, 86% in Swiss mice and 92, 94 and 89% in male Swiss bare mice respectively. Hydroxychavicol showed 90% inhibition in Swiss bare mice at 24 weeks of treatment. Eugenol showed minimal protection in both strains of mice. The mean latency period and survivors in BLE, beta-carotene, alpha-tocopherol and hydroxychavicol treated groups were remarkably high as compared to DMBA alone treated group. Intraperitoneal injection of betal leaf constituents showed a significant effect on both glutathione and glutathione S-transferase levels in the Swiss mouse skin.     

Chemopreventive effects of coffee bean and rice constituents on colorectal carcinogenesis

Polyphenolic compound chlorogenic acid (CGA) known to be much contained in coffee beans was found to have a regressive effect on induced aberrant crypt foci (ACF) as well as on development of ACF in azoxymethane (AOM)-induced colorectal carcinogenesis in rats. Rice germ and gamma-aminobutyric acid-enriched defatted rice germ inhibited AOM-induced ACF formation and colorectal carcinogenesis in rats. Ferulic acid (FA) also known to be contained in coffee beans and rice prevented AOM-induced ACF formation and intestinal carcinogenesis in rats. Both of food factors, coffee and rice may be of benefit to prevention of human colorectal cancers.     

Chemopreventive effects of hydroxymatairesinol on uterine carcinogenesis in Donryu rats

Hydroxymatairesinol (HMR), obtained from the heartwood of spruce (Picea abies), has been demonstrated to exert chemo-preventive effects on the development of mammary tumors in rats. To examine the influence of HMR on uterine carcinogenesis, adult Donryu rats were initiated with a single intrauterine treatment of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at 11 weeks of age and fed thereafter 0, 200, or 600 ppm HMR mixed in the soy-containing diet until 15 months of age. Incidences of uterine adenocarcinoma in both 200 and 600 ppm HMR-dosed groups were significantly reduced to 11% and 15%, respectively, less than 50% of 0 ppm, at the end of the experiment (P < 0.05). A delay in the start of persistent estrus by HMR was observed at 8 months of age compared with controls given carcinogen alone. From urinalysis, HMR was metabolized mainly to enterolactone and hydroxyenterolactone. These findings suggest that HMR or its metabolites exert chemo-preventive effects in the rat ENNG-uterine carcinogenesis model.     

Chemopreventive effect of diclofenac on mammary carcinogenesis in Sprague-Dawley rats

Chemopreventive effect of non-steroidal antiinflammatory drugs (NSAIDs) in mammary carcinogenesis was reported in several studies. In this study, the effect of a nonselective cyclooxygenase inhibitor diclofenac (DICLO) in the prevention of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis in Sprague-Dawley female rats was evaluated. NMU was administered to animals intraperitoneally in two doses of 50 mg kg^?1 b.w. within postnatal days 42-48. In experiment A (short-term administration), DICLO was administrated intramuscularly (5 mg kg^?1 b.w.) every other day, starting 3 days before and for subsequent 25 days after first NMU injection. In experiment B (long-term administration), DICLO was administered in tap water (0.01 mg ml^?1) continually, starting 7 days before and for subsequent 22 weeks after first NMU dose. The study was terminated 22 weeks after the first dose of NMU in both experiments. After DICLO treatment, tumor frequency per group was reduced in both variants of drug administration: in experiment A by 38% and in experiment B by 39.5%. Moreover, DICLO decreased tumor incidence by 11.5% and delayed tumor latency by 14 days in experiment B. In our preventive-curative experiments DICLO decreased some parameters of NMU-induced rat mammary carcinogenesis, mainly the tumor frequency.     

Chemopreventive efficacy of green tea drinking against 1,2‐dimethyl hydrazine‐induced rat colon carcinogenesis

Colorectal cancer is one of the leading causes of tumour‐related deaths. In the present study, the chemopreventive effect of green tea on 1,2‐dimethylhydrazine (DMH)‐induced colon carcinogenesis was studied in male Wistar rats. The DMH group received subcutaneous injections of DMH (30 mg kg^?1 body weight) once a week for 30 weeks, the normal group received the vehicle of DMH, and the DMH + green tea group received DMH simultaneously with 1% green tea as their sole source of drinking fluid throughout the experimental period. In the DMH group treated with green tea, significant reductions in gene overexpressions of colonic nuclear factor κB (NF‐κB), tumour necrosis factor α, inducible nitric oxide synthase and cyclooxygenase 2, and NF‐κB immunostaining indicates the anti‐inflammatory effect of green tea in attenuating colon cancer. Moreover, the anti‐angiogenic and anti‐invasiveness effects of green tea were revealed as reductions of both vascular endothelial growth factor and matrix metalloproteinase‐7 mRNA expression levels. These effects were confirmed by the significant reduction of serum tumour necrosis factor α, C‐reactive protein levels, inhibition of tumour incidence, and nearly normal survival rate and colonic architecture. It can be concluded that green tea exerts a potent chemopreventive effect on colon carcinogenesis possibly due to the inhibition of NF‐κB. Copyright © 2012 John Wiley & Sons, Ltd.     

Chemopreventive potential of luteolin during colon carcinogenesis induced by 1,2-dimethylhydrazine

We investigated the chemopreventive potential of luteolin on hepatic and circulatory lipid peroxidation and antioxidant status during 1,2-dimethylhydrazine induced colon carcinogenesis in rats. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given at the initiation and also at the postinitiation stages of carcinogenesis to DMH treated rats. The animals were sacrificed at the end of 30 weeks. Enhanced lipid peroxidation in the liver and circulation of tumor bearing rats was accompanied by a significant decrease in the levels of plasma and hepatic reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), vitamin C, vitamin E and beta-carotene in DMH treated rats as compared to the control rats. Intragastric administration of luteolin (0.2mg/kg body weight) to DMH-treated rats significantly reduced the incidence and size of tumor in the colon, reduced lipid peroxidation levels and enhanced the plasma and hepatic activities of GSH, GPx, GST, GR, SOD, CAT, vitamin C, vitamin E and beta-carotene. Thus the chemopreventive efficacy of luteolin against colon carcinogenesis is evidenced by our preliminary studies which showed decreased incidence of tumors and the antiperoxidative and antioxidant effect of luteolin. Further study on the exact mechanism of action of luteolin in preventing colon carcinogenesis is yet to be elucidated.