Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice

The genotoxic potential of anti-tumor drugs limits their efficacy in the treatment of cancers. Since ancient times, saffron (dried stigmas of Crocus sativus L.) has been used as a spice and medicinal herb. Saffron is a rich source of carotenoids and is known for its anti-cancer and antitumor properties. The present study was designed to ascertain the chemoprotective potential of saffron against the genotoxicity of three well-known anti-tumor drugs-cisplatin (CIS), cyclophosphamide (CPH) and mitomycin C (MMC)-using comet assay. Three doses of saffron (20, 40 and 80 mg/kg b.w.) were orally administered to mice for five consecutive days prior to the administration of anti-tumor drugs under investigation. Pre-treatment with saffron significantly inhibited anti-tumor drugs induced cellular DNA damage (strand breaks) as revealed by decreased comet tail length, tail moment and percent DNA in the tail. These findings, together with our previous results, suggest a potential role for saffron as an anti-genotoxic, anti-oxidant and chemopreventive agent and could be used as an adjuvant in chemotherapeutic applications.

[1]  H. Riese,et al.  Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rat. , 1999, Nutrition and cancer.

[2]  S. K. Abraham,et al.  Protective effects of saffron (Crocus sativus Linn.) on genotoxins‐induced oxidative stress in Swiss albino mice , 2003, Phytotherapy research : PTR.

[3]  L. Wattenberg,et al.  Glutathione S-transferase activity: enhancement by compounds inhibiting chemical carcinogenesis and by dietary constituents. , 1982, Journal of the National Cancer Institute.

[4]  K. Panikkar,et al.  Antitumour activity of saffron (Crocus sativus). , 1991, Cancer letters.

[5]  S. K. Abraham,et al.  Anti-genotoxicity and glutathione S-transferase activity in mice pretreated with caffeinated and decaffeinated coffee. , 1999, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[6]  A. Quintanilha,et al.  CRC Handbook of free radicals and antioxidants in biomedicine , 1989 .

[7]  L. Wattenberg.  Chemoprevention of cancer. , 1996, Preventive medicine.

[8]  L. Bjeldanes,et al.  Effects of commonly consumed vegetables on hepatic xenobiotic-metabolizing enzymes in the mouse. , 1985, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[9]  B. Stavric.  Antimutagens and anticarcinogens in foods. , 1994, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[10]  P. Tandon,et al.  cis-Dichlorodiammine platinum(II) induced aberrations in mouse bone-marrow chromosomes. , 1985, Mutation research.

[11]  K. Panikkar,et al.  Effect of saffron on thymocyte proliferation, intracellular glutathione levels and its antitumor activity. , 1992, BioFactors.

[12]  T. Tseng,et al.  Crocetin protects against oxidative damage in rat primary hepatocytes. , 1995, Cancer letters.

[13]  R. North.  Down-regulation of the antitumor immune response. , 1985, Advances in cancer research.

[14]  Wattenberg Lw.  Inhibition of neoplasia by minor dietary constituents. , 1983, Cancer research.

[15]  D. Harnden,et al.  Catalog of Chromosome Aberrations in Cancer , 1989 .

[16]  M. Manfait,et al.  Inhibition of growth and induction of differentiation of promyelocytic leukemia (HL-60) by carotenoids from Crocus sativus L. , 1994, Anticancer research.

[17]  F. Abdullaev.  Biological effects of saffron. , 1993, BioFactors.

[18]  A. E. Rogers,et al.  Diet and carcinogenesis. , 1993, Carcinogenesis.

[19]  L. Ferguson.  Antimutagens as cancer chemopreventive agents in the diet. , 1994, Mutation research.

[20]  K. Panikkar,et al.  Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice. , 1991, Nutrition and cancer.

[21]  S. Lippard,et al.  Binding of the antitumor drug cis-diamminedichloroplatinum(II) (cisplatin) to DNA. , 1985, Biochimica et biophysica acta.

[22]  H. Renner.  In vivo effects of single or combined dietary antimutagens on mutagen-induced chromosomal aberrations. , 1990, Mutation research.

[23]  J. Bhat,et al.  Riboflavine and Thiamine Contents of Saffron, Crocus sativus Linn. , 1953, Nature.

[24]  C. Ramel.  Inhibitors of mutagenesis and their relevance to carcinogenesis. , 1986, Basic life sciences.

[25]  F. Mitelman,et al.  Catalog of Chromosome Aberrations in Cancer , 1996, British Journal of Cancer.

[26]  G. Alonso,et al.  Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. , 1996, Cancer letters.

[27]  B. Ketterer.  Protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis. , 1988, Mutation research.

[28]  S C Nair,et al.  Saffron chemoprevention in biology and medicine: a review. , 1995, Cancer biotherapy.

[29]  F. Abdullaev,et al.  The effect of saffron on intracellular DNA, RNA and protein synthesis in malignant and non-malignant human cells. , 1992, BioFactors.

[30]  B. Ames,et al.  Inhibitors of mutagenesis and their relevance to carcinogenesis , 1986 .

[31]  C. Wang,et al.  Effects of crocetin on the hepatotoxicity and hepatic DNA binding of aflatoxin B1 in rats. , 1991, Carcinogenesis.

[32]  R. Tice,et al.  A simple technique for quantitation of low levels of DNA damage in individual cells. , 1988, Experimental cell research.

[33]  S. K. Abraham,et al.  Inhibitory effects of dietary vegetables on the in vivo clastogenicity of cyclophosphamide. , 1986, Mutation research.

[34]  B. Vig.  Genetic toxicology of mitomycin C, actinomycins, daunomycin and adriamycin. , 1977, Mutation research.

[35]  G. Stoner,et al.  Cancer chemoprevention: principles and prospects. , 1993, Carcinogenesis.

[36]  V. Steele,et al.  Screening of potential chemopreventive agents using biochemical markers of carcinogenesis. , 1994, Cancer research.

[37]  S. K. Abraham,et al.  INHIBITION OF GENOTOXICITY BY SAFFRON (CROCUS SATIVUS L.) IN MICE , 2001, Drug and chemical toxicology.

[38]  B. Ames,et al.  International Commission for Protection Against Environmental Mutagens and Carcinogens. ICPEMC Publication No. 12. Inhibitors of mutagenesis and their relevance to carcinogenesis. Report by ICPEMC Expert Group on Antimutagens and Desmutagens. , 1986, Mutation research.

[39]  P. Kupradinun,et al.  Antimutagenic and anticarcinogenic potentials of some Thai vegetables. , 1998, Mutation research.