The Chemopreventive Effect of Nigella Sativa on 1,2-dimethylhydrazine-induced Colon Tumor

In this study, the chemopreventive efficacy of Nigella sativa seed powder as an important chemopreventive herb on the formation of colon tumor has been examined through measuring the levels of hepatic oxidative stress and metabolizing enzymes in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats. Male Wistar rats were divided into 6 groups as untreated control, Sham, DMH (30mg/kg b.w) received carcinogen via subcutaneously (s.c) injection once a week for 18 weeks and treatment groups received diet containing Nigella sativa (2 and 4%) until the end of whole experimental period of 6 months. It is indicated that Nigella sativa seed powder could prevent colon tumor formation by modulating the activities of hepatic detoxification enzymes, GST and CYP450 whereas antioxidant statues are not affected. The data was confirmed by histopathological findings It is obvious that one of the mechanisms of chemoprevention of colon tumorigenesis by Nigella sativa seed powder may be the enhancement of carcinogen detoxification but not antioxidant system in the liver.

[1]  T. Mahjoub,et al.  Thymoquinone, the Nigella sativa Bioactive Compound, Prevents Circulatory Oxidative Stress Caused by 1,2-Dimethylhydrazine in Erythrocyte during Colon Postinitiation Carcinogenesis , 2012, Oxidative medicine and cellular longevity.

[2]  J. Ashrafi-Helan,et al.  Effect of dietary caraway essential oils on expression of β-catenin during 1,2-dimethylhydrazine-induced colonic carcinogenesis , 2012, Journal of Natural Medicines.

[3]  S. Ehsan,et al.  Thymoquinone rich fraction from Nigella sativa and thymoquinone are cytotoxic towards colon and leukemic carcinoma cell lines. , 2011 .

[4]  T. Mauriala,et al.  Impact of protein binding on the analytical detectability and anticancer activity of thymoquinone , 2011, Journal of chemical biology.

[5]  A. Allameh,et al.  Inhibitory Effects of Dietary Caraway Essential Oils on 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis is Mediated by Liver Xenobiotic Metabolizing Enzymes , 2010, Nutrition and cancer.

[6]  I. Al-Saleh,et al.  Role of Nigella sativa and a number of its antioxidant constituents towards azoxymethane‐induced genotoxic effects and colon cancer in rats , 2008, Phytotherapy research : PTR.

[7]  J. Rautio,et al.  Cytochrome P450-activated prodrugs: targeted drug delivery. , 2008, Current medicinal chemistry.

[8]  L. Rodrigo,et al.  Colonic perianastomotic carcinogenesis in an experimental model , 2008, BMC Cancer.

[9]  Aamir Ahmad,et al.  From here to eternity - the secret of Pharaohs: Therapeutic potential of black cumin seeds and beyond. , 2008, Cancer therapy.

[10]  M. A. Kamal,et al.  Anti-tumor properties of blackseed (Nigella sativa L.) extracts. , 2007, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[11]  N. Nalini,et al.  Modulatory influence of dietary resveratrol during different phases of 1,2-dimethylhydrazine induced mucosal lipid-peroxidation, antioxidant status and aberrant crypt foci development in rat colon carcinogenesis. , 2006, Biochimica et biophysica acta.

[12]  N. Nalini,et al.  Dose dependent inhibitory effect of dietary caraway on 1,2-dimethylhydrazine induced colonic aberrant crypt foci and bacterial enzyme activity in rats , 2006, Investigational New Drugs.

[13]  A. Allameh,et al.  Changes in hepatic cytosolic glutathione S-transferase activity and expression of its class-P during prenatal and postnatal period in rats treated with aflatoxin B1 , 2006, Archives of Toxicology.

[14]  N. Nalini,et al.  Chemopreventive efficacy of ginger, a naturally occurring anticarcinogen during the initiation, post-initiation stages of 1,2 dimethylhydrazine-induced colon cancer. , 2005, Clinica chimica acta; international journal of clinical chemistry.

[15]  K. Schramm,et al.  Suppressive effects of caraway (Carum carvi) extracts on 2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin-dependent gene expression of cytochrome P450 1A1 in the rat H4IIE cells. , 2005, Toxicology in vitro : an international journal published in association with BIBRA.

[16]  V. Balasubramaniyan,et al.  Rat colonic lipid peroxidation and antioxidant status: the effects of dietary luteolin on 1,2-dimethylhydrazine challenge. , 2005, Cellular & molecular biology letters.

[17]  R. Schneider-Stock,et al.  Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. , 2004, International journal of oncology.

[18]  A. Gilani,et al.  A Review of Medicinal Uses and Pharmacological Activities of Nigella sativa , 2004 .

[19]  A. Ghannadi,et al.  Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug , 2004, Phytotherapy research : PTR.

[20]  R. Malekzadeh,et al.  Cancer occurrence in Ardabil: Results of a population‐based Cancer Registry from Iran , 2003, International journal of cancer.

[21]  S. Fukushima,et al.  Chemopreventive Potential of Volatile Oil From Black Cumin (Nigella sativa L.) Seeds Against Rat Colon Carcinogenesis , 2003, Nutrition and cancer.

[22]  P. Dudrick,et al.  In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone. , 2003, International journal of oncology.

[23]  S. Moselhy,et al.  Inhibition of methylnitrosourea (MNU) induced oxidative stress and carcinogenesis by orally administered bee honey and Nigella grains in Sprague Dawely rats. , 2002, Journal of experimental & clinical cancer research : CR.

[24]  T. Devasena,et al.  Bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione (a curcumin analog) ameliorates DMH-induced hepatic oxidative stress during colon carcinogenesis. , 2002, Pharmacological research.

[25]  R. Mironova,et al.  [Microbiological degradation of asymmetrical dimethylhydrazine--a toxic component of rocket fuel]. , 2000, Prikladnaia biokhimiia i mikrobiologiia.

[26]  F. Khanum,et al.  Anticarcinogenic effects of curry leaves in dimethylhydrazine-treated rats , 2000, Plant foods for human nutrition.

[27]  Taylor Murray,et al.  Cancer statistics, 2000 , 2000, CA: a cancer journal for clinicians.

[28]  T. Wobbes,et al.  Polymorphic expression of the glutathione S-transferase P1 gene and its susceptibility to Barrett's esophagus and esophageal carcinoma. , 1999, Cancer research.

[29]  G. Choudhary,et al.  Human health perspective on environmental exposure to hydrazines: a review. , 1998, Chemosphere.

[30]  W. Peters,et al.  Effects of dietary anticarcinogens on rat gastrointestinal glutathione peroxidase activity. , 1998, Oncology reports.

[31]  G. Alink,et al.  Effects of a vegetables-fruit mixture on liver and colonic 1,2-dimethylhydrazine-metabolizing enzyme activities in rats fed low- or high-fat diets. , 1998, Cancer letters.

[32]  Takuji Tanaka,et al.  Citrus auraptene exerts dose-dependent chemopreventive activity in rat large bowel tumorigenesis: the inhibition correlates with suppression of cell proliferation and lipid peroxidation and with induction of phase II drug-metabolizing enzymes. , 1998, Cancer research.

[33]  M. Moghadasian,et al.  Endogenous antioxidant status in neoplastic and adjacent tissues in 1,2-dimethylhydrazine-induced colon cancer in rats: effects of olsalazine. , 1996, Carcinogenesis.

[34]  M. Wargovich,et al.  Chemopreventive effect of S-allylcysteine and its relationship to the detoxification enzyme glutathione S-transferase. , 1996, Carcinogenesis.

[35]  D. Rosenberg,et al.  A comparative study of hepatic and colonic metabolic enzymes in inbred mouse lines before and after treatment with the colon carcinogen, 1,2-dimethylhydrazine. , 1996, Drug metabolism and disposition: the biological fate of chemicals.

[36]  A. Kulkarni,et al.  Retinoids inhibit mammalian glutathione transferases. , 1995, Cancer letters.

[37]  Dong-Hyun Kim,et al.  Protective roles of mushrooms in experimental colon carcinogenesis , 1995 .

[38]  J. Yodoi,et al.  Persistent oxidative stress in cancer , 1995, FEBS letters.

[39]  R. Perry,et al.  Glutathione levels and variability in breast tumors and normal tissue , 1993, Cancer.

[40]  K. Panikkar,et al.  Antitumour principles from Nigella sativa seeds. , 1992, Cancer letters.

[41]  B. Pence,et al.  Rat colonic antioxidant status: interaction of dietary fats with 1,2-dimethylhydrazine challenge. , 1992, The Journal of nutrition.

[42]  Y. Sun,et al.  Free radicals, antioxidant enzymes, and carcinogenesis. , 1990, Free radical biology & medicine.

[43]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.

[44]  T. Galeotti,et al.  Lipid peroxidation in tumour cells. , 1988, Free radical biology & medicine.

[45]  E. Fiala,et al.  Effects of chronic dietary ethanol on in vivo and in vitro metabolism of methylazoxymethanol and on methylazoxymethanol-induced DNA methylation in rat colon and liver. , 1987, Cancer research.

[46]  S. Leveson,et al.  Free radical detoxifying systems in human colorectal cancer. , 1985, British Journal of Cancer.

[47]  W. Gunn.  Cancer: Principles and Practice of Oncology , 1982 .

[48]  R. Gittes,et al.  Potentiation of dimethylhydrazine bowel carcinogenesis in rats , 1981, Cancer.

[49]  R. Gittes,et al.  Potentiation of 1-2-dimethylhydrazine-induced bowel carcinogenesis by the urinary bladder carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. , 1980, Carcinogenesis.

[50]  V. Babayan,et al.  PROXIMATE ANALYSIS, FATTY ACID AND AMINO ACID COMPOSITION OF NIGELLA SATIVA L. SEEDS , 1978 .

[51]  E. Fiala.  Investigations into the metabolism and mode of action of the colon carcinogen 1, 2‐dimethylhydrazine , 1975, Cancer.

[52]  N. G. Kovaleva,et al.  [Medicinal plants]. , 1954, Aptechnoe delo.