Sukta Das

Saffron suppresses oxidative stress in DMBA-induced skin carcinoma: A histopathological study

Cancer chemoprevention is the use of natural, synthetic or biological substances to reverse or prevent the development of cancer. Saffron is a naturally derived plant product that acts as an antispasmodic, diaphoretic, carminative, emmenagogic and sedative. Our aim in this study was to investigate the chemopreventive effect of aqueous saffron on chemically induced skin carcinogenesis using a histopathological approach. Mice were divided into five groups: carcinogen control (CC), normal control (NC) and saffron-treated Groups A, B and C. Groups A, B, C and CC mice received three topical applications of 7,12 dimethylbenz[a]anthracene (DMBA) followed by croton oil on shaven dorsal skin for 8 weeks. NC mice received topical skin applications of the vehicle, acetone, only. Saffron infusion was fed orally to three groups of mice either before (Group A) or after (Group C) or both before and after (Group B) DMBA applications. The activities of antioxidant enzymes glutathione-S transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in liver tissue samples taken at 0, 6, 10 and 12 weeks from all groups were assessed. Standard histological examination of skin demonstrated a beneficial action of saffron in mice where saffron treatments were given both before and after the induction of skin carcinogenesis. Saffron ingestion inhibited the formation of skin papillomas in animals and simultaneously reduced their size. In conclusion, saffron inhibits DMBA-induced skin carcinoma in mice when treated early. This may be due, at least in part, to the induction of cellular defense systems.

Vitamin E in the genesis and prevention of cancer. A review.

A review of current literature reveals that the relationships between vitamin E and cancer is not yet fully understood though many experimental and clinical studies have shown that vitamin E can protect against carcinogenesis and tumour growth. This vitamin also appears to reduce toxicity of several anticancer therapies. Such effects are probably due to the antioxidant property and immunomodulatory function of vitamin E. The findings of different groups suggest that this vitamin may be helpful as a cancer chemopreventive agent.

Prevention of carcinogen-induced mouse skin papilloma by whole fruit aqueous extract of Momordica charantia.

The anticarcinogenic effect of aqueous extract of fruit of Momordica charantia (bitter gourd), which is widely used as a vegetable in India, was studied in a two-step skin carcinogenesis model in mice. The possible mode of action was also investigated. Oral administration of the fruit extract was found to have an adverse effect on the general health and lifespan of the animals when used at a high concentration. But when this dose was reduced by half, the test extract afforded protection from the development of skin tumour and increased life expectancy. Carcinogen-induced lipid peroxidation in liver and DNA damage in lymphocytes were found to be reduced following treatment with Momordica. The fruit extract was found to significantly activate the liver enzymes glutathione-S-transferase, glutathione peroxidase and catalase (P < 0.001), which showed a depression following exposure to the carcinogen. The results suggest a preventive role of water-soluble constituents of M. charantia fruit during carcinogenesis, which is mediated possibly by their modulatory effect on enzymes of the biotransformation and detoxification system of the host.

Plant Lectins as Inhibitors of Tumour Growth and Modulators of Host Immune Response

The antitumour activities of four plant lectins, phytohaemagglutinin, pokeweed mitogen, soybean agglutinin, and wheat germ agglutinin, were evaluated on a murine ascitic lymphoma. The effects of lectin treatment on mitogenic response of peripheral blood lymphocytes and macrophage-mediated tumour cell lysis were also assessed. All four lectins studied were found to be able to restrict tumour growth and to improve the life expectancy of the host. The response of peripheral blood lymphocytes towards mitogenic stimulation was found to be improved and enhancement of tumour cytolysis by peritoneal macrophages was noted following lectin treatment.

Experimental Evaluation of Preventive and Therapeutic Potentials of Lysozyme

Therapeutic efficacy and preventive role of egg white lysozyme was evaluated in three types of murine ascitic tumours, namely sarcoma 180, Ehrlichs carcinoma, and Daltons lymphoma. Lysozyme treatment produced regression of tumour growth and improved the life expectancy of the host. Growth of tumour cells treated in vitro with lysozyme prior to transplantation was also affected. In addition, lysozyme was found to have a preventive effect when administered to normal mice. The antitumour activity, therapeutic and preventive, of lysozyme seems to be due to its action on the tumour cell surface as well as on the host-mediated immune response.

Chemopreventive activity of quercetin during carcinogenesis in cervix uteri in mice

The chemopreventive action of quercetin was examined during 20‐methyl cholanthrene induced cervical neoplasia in virgin Swiss albino mice. The effects were evaluated on the basis of histopathological observation of the cervical epithelium, micronucleus frequency in vaginal exfoliated cells and some biochemical parameters in the host liver. Quercetin was found to arrest or reverse the progression of cervical neoplasia. The micronucleus frequency was reduced following its administration. The potential anti‐carcinogenic effect of quercetin noted in this study is attributed to its antioxidant property which was reflected in the lipid peroxides and their role in the host detoxification system, as expressed in liver glutathione level, glutathione‐S‐transferase, glutathione peroxidase, catalase and superoxide dismutase activity. As an integral part of the diet quercetin may offer protection to the epithelium from the damaging effects of carcinogenic chemicals. Copyright

Tea polyphenols can restrict benzo[a]pyrene-induced lung carcinogenesis by altered expression of p53-associated genes and H-ras, c-myc and cyclin D1

The modulatory influence of tea polyphenols (epigallocatechin gallate, epicatechin gallate and theaflavin) on benzo[a]pyrene (B[a]P)-induced lung carcinogenesis in mice was analyzed using histopathological and molecular parameters. Progression of lung lesions was restricted at the hyperplastic stage by tea polyphenols. A significant reduction in cellular proliferative index and an increase in apoptotic index were noted in the restricted lung lesions. High expression of H-ras, c-myc, cyclin D1 and p53 genes was seen at the inflammatory stage (9th week) and in subsequent premalignant lesions, but down-regulation of H-ras at the hyperplastic stage (17th week). Expression of bcl-2 was high in hyperplastic lesions, whereas the expression of mdm2 and bcl-xl increased only at the moderately dysplastic stage (36th week). The tea polyphenols inhibited inflammatory response in the lung lesions on the 9th week, when decreased expression of H-ras and c-myc and increased expression of bax were noted. Prolonged treatment (>9th week) with tea polyphenols resulted in changes in the expression of some additional genes, such as reduced expression of cyclin D1 (from the 17th week), bcl-2 (from the 26th week; mild dysplasia) and p21 (on the 36th week), and high expression of p53 (from the 17th week) and p27 (on the 36th week). These observations indicate that the tea polyphenols can restrict B[a]P-induced lung carcinogenesis by differential modulation of the expression of p53 and its associated genes such as bax, bcl-2, mdm2, p21 and p27, along with H-ras, c-myc and cyclin D1, at different time points.

Eugenol restricts DMBA croton oil induced skin carcinogenesis in mice: Downregulation of c-Myc and H-ras, and activation of p53 dependent apoptotic pathway

BACKGROUND Eugenol is the active component of essential oil isolated from clove (Syzigium aromaticum). Eugenol has antimutagenic, antigenotoxic, anti-inflammatory properties. The anticarcinogenic effect of eugenol was evident in different types of cell lines. However, its anticarcinogenic effect in in vivo has not yet been fully explored. OBJECTIVE The aim of this study is to evaluate the chemopreventive potential of eugenol in an experimental skin carcinogenesis mice model system. METHOD Skin tumor was induced by topical application of DMBA croton oil in Swiss mice. To assess the chemopreventive potential of eugenol, it was orally administered 15 days prior carcinogen treatment. The development of skin carcinogenesis was confirmed by histopathological analysis. Cellular proliferation and apoptosis in the skin tumor were analyzed by in situ cellular proliferation and in situ cell death assay. Expression of some proliferation and apoptosis associated genes was analyzed by RT-PCR and protein expression was analyzed by Western blot. RESULTS Reduction in incidence and sizes of skin tumors along with overall increase in survival of mice were seen due to eugenol treatment. Restriction of skin carcinogenesis at the dysplastic stage along with reduced rate of cellular proliferation and increase in apoptosis were evident in eugenol treated skin tumors. Eugenol treatment led to the downregulation of c-Myc, H-ras and Bcl2 expression along with upregulation of P53, Bax and active Caspase-3 expression in the skin lesions. CONCLUSION Restriction of skin carcinogenesis at dysplastic stage by eugenol was due to attenuation of c-Myc, H-ras and modification of some p53 associated gene expression.

Prevention of liver carcinogenesis by amarogentin through modulation of G1/S cell cycle check point and induction of apoptosis.

Amarogentin, a secoiridoid glycoside, is an active component of the medicinal plant Swertia chirata. In this study, chemopreventive and chemotherapeutic actions of amarogentin were evaluated in a carbon tetrachloride (CCl(4))/N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis mouse model system during continuous and posttreatment schedule. Better survival, no toxicity and increased body weight were noted in amarogentin-treated mice. Reduction in proliferation and increase in apoptosis frequency were evident in amarogentin-treated groups. In carcinogen control group moderate dysplasia, severe dysplasia and hepatocellular carcinoma were evident at 10th, 20th and 30th week, respectively. Amarogentin was found to prevent progression of liver carcinogenesis at mild dysplastic stage. Exposure to CCl(4)/NDEA resulted in upregulation of ppRb807/811, cyclinD1 and cdc25A at 10th week and additional activation of cMyc and mdm2 along with downregulation of LIMD1, p53 and p21 at 20th week. This was followed by activation of ppRb567 and downregulation of Rbsp3 at 30th week. Prevention of carcinogenesis by amarogentin in both groups might be due to cumulative upregulation of LIMD1, RBSP3, p16 and downregulation of cdc25A at 10th week along with activation of p53 and p21 and downregulation of ppRb807/811 and ppRb567 at 20th week, followed by downregulation of cyclinD1, cMyc and mdm2 at 30th week. During carcinogenesis reduction of apoptosis was evident since 20th week. However, amarogentin treatment could significantly induce apoptosis through upregulation of the Bax-Bcl2 ratio, activation of caspase-3 and poly ADP ribose polymerase cleavage. This is the first report of chemopreventive/therapeutic role of amarogentin during liver carcinogenesis through modulation of cell cycle and apoptosis.

Inhibition of DMBA/croton oil-induced two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate.

Selenium, an essential micronutrient, is associated with antioxidant functions, physiological defence mechanisms against different diseases including several types of cancers. Search for new selenium compounds with more chemopreventive activities and lesser toxicities are in progress. In the present study, the antioxidative roles of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated against 7,12-dimethylbenz(a)anthracene (DMBA)/croton oil-induced two-stage mouse skin carcinogenesis model. The compound was administered orally in carcinogen-induced mice in two different non-toxic doses: 2 mg/kg body weight and 3 mg/kg body weight. Significant inhibition in the incidence of papilloma formation (58–80%) as well as in the cumulative number of papilloma per papilloma-bearing mouse were observed in the treated groups as compared with the carcinogen control group. The compound was also found to significantly upregulate different phase II detoxifying enzymes in liver cytosol such as glutathione-S-transferase (P<0.01), catalase (P<0.01) and superoxide dismutase (SOD) (P<0.01) when measured after 15 days and also after 12 weeks of first DMBA treatment. Lipid peroxidation measured as the thiobarbituric acid reactive substances in liver microsomes was significantly inhibited (P<0.05) in a dose-dependent manner by diphenylmethyl selenocyanate. Thus the compound exerts its chemopreventive activity by reducing papilloma formation during chemically induced carcinogenesis, which in turn, may be through modulating the level of lipid peroxidation and phase II detoxifying enzyme system at the doses evaluated.