[01] Zahide E. Durak, Ordu University, Central Research Laboratory, Ordu, Turkey. [02] Suleyman Buber, Ankara University Medical Faculty, Department of Biochemistry, Ankara, Turkey. [03] Ender H. Kocaoglu, Ankara University Medical Faculty, Surgical Oncology Department, Ankara, Turkey. [04] Bahadir Ozturk, Selçuk University Medical Faculty, Department of Biochemistry, Konya, Turkey.

Background and Aim: Cancer is the major problem for all people in the world. The scientists have long been looking to natural remedies for the treatment of cancer because of side effects of chemotherapy and radiotherapy. Therefore we aimed to investigate possible effects of aquoeus extracts of Celandine (Chelidonium majus), Red Clover (Trifolium pratense), Flax seed (Linum usitatissimum) and Coriander (Coriandrum sativum) on adenosine deaminase (ADA) activity in cancerous and non cancerous human gastric and colon tissues. Materials and Methods: Cancerous and non cancerous human gastric (n=31) and colon tissues (n=19) removed by surgical operations were studied. The extracts were prepared in distilled water. Tissues were first homogenized in saline solution (20%, w/v), then centrifuged and supernatant fraction was used. In the tissue samples, adenosine deaminase activities were measured with and without plant extracts preincubated for 1 h. Results: It has been observed that aquoeus extracts of celandine, red clover, flax seed and coriander inhibit ADA enzyme in cancerous gastric tissues significantly, but none affects the enzyme in noncancerous gastric tissue. In the colon tissues, none of those except celandine affects the ADA activity. Celandine however activates the enzyme in both colon tissues significantly. Conclusion: It has been suggested that inhibition of ADA enzyme by celandine, red clover, flax seed and coriander extracts might give selective advantage to the cancerous tissues to combat cancer process. Clarification of ADA activation in colon tissues by celandine extract however needs further studies.

Adenosine Deaminase, Cancer, Colon Tissue, Gastric Tissue, Chelidonium maju, Trifolium pratense, Linum usitatissimum, Coriandrum sativum

[01] Abdulla M, Gruber P. Role of diet modification in cancer prevention. BioFactors (Oxford, England). 2000; 12 (1-4):45-51. [02] Wiseman M. The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Proceedings of the Nutrition Society. 2008; 67 (03):253-6. [03] Wilson DK, Rudolph FB, Quiocho FA. Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations. Science (New York, NY). 1991; 25 2(5010):1278-84. [04] Cristalli G, Costanzi S, Lambertucci C, Lupidi G, Vittori S, Volpini R, et al. Adenosine deaminase: functional implications and different classes of inhibitors. Medicinal research reviews. 2001; 21 (2):105-28. [05] Aghaei M, Karami-Tehrani F, Salami S, Atri M. Adenosine deaminase activity in the serum and malignant tumors of breast cancer: the assessment of isoenzyme ADA1 and ADA2 activities. Clinical biochemistry. 2005; 38 (10):887-91. [06] Glazer RI. Adenosine deaminase inhibitors: their role in chemotherapy and immunosuppression. Cancer Chemother Pharmacol. 1980; 4(4):227-35. [07] Brown JB, Lee G, Grimm GR, Barrett TA. Therapeutic benefit of pentostatin in severe IL-10-/- colitis. Inflammatory bowel diseases. 2008; 14 (7):880-7. [08] Nadova S, Miadokova E, Alfoldiova L, Kopaskova M, Hasplova K, Hudecova A, et al. Potential antioxidant activity, cytotoxic and apoptosis-inducing effects of Chelidonium majus L. extract on leukemia cells. Neuro endocrinology letters. 2008; 29 (5):649-52. [09] Taborska E, Bochorakova H, Dostal J, Paulova H. [The greater celandine (Chelidonium majus L.)--review of present knowledge]. Ceska a Slovenska farmacie: casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti. 1995; 44 (2):71-5. [10] Kim DS, Kim SJ, Kim MC, Jeon YD, Um JY, Hong SH. The therapeutic effect of chelidonic acid on ulcerative colitis. Biological & pharmaceutical bulletin. 2012; 35 (5):666-71. [11] Chevallier A, Association RsD. The encyclopedia of medicinal plants: Dorling Kindersley London; 1996; p. 185. [12] Howard M. Traditional folk remedies: a comprehensive herbal: Century; Ebury Press. 1987; pp. 146–147. [13] Yang G, Lee K, Lee MH, Kim SH, Ham IH, Choi HY. Inhibitory effects of Chelidonium majus extract on atopic dermatitis-like skin lesions in NC/Nga mice. Journal of ethnopharmacology. 2011; 138 (2):398-403. [14] Rogelj B, Popovic T, Ritonja A, Strukelj B, Brzin J. Chelidocystatin, a novel phytocystatin from Chelidonium majus. Phytochemistry. 1998; 49 (6):1645-9. [15] Wang L, Waltenberger B, Pferschy-Wenzig EM, Blunder M, Liu X, Malainer C, et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARgamma): a review. Biochemical pharmacology. 2014; 92 (1):73-89. [16] Roberts DW, Doerge DR, Churchwell MI, Gamboa da Costa G, Marques MM, Tolleson WH. Inhibition of extrahepatic human cytochromes P450 1A1 and 1B1 by metabolism of isoflavones found in Trifolium pratense (red clover). J Agric Food Chem. 2004; 52 (21):6623-32. [17] Pan A, Yu D, Demark-Wahnefried W, Franco OH, Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. The American journal of clinical nutrition. 2009; 90 (2):288-97. [18] Thompson LU, Chen JM, Li T, Strasser-Weippl K, Goss PE. Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res. 2005; 11 (10):3828-35. [19] McGee H. Cilantro haters, it's not your fault. The New York Times, New York City. 2010; 1. [20] Afifi N, Ramadan A, El Kashoury E, El Banna H. Some pharmacological activities of essential oils of certain umbelliferous fruits. Veterinary Medical Journal Giza, Cairo Univ. 1994. [21] Chithra V, Leelamma S. Coriandrum sativum--effect on lipid metabolism in 1, 2-dimethyl hydrazine induced colon cancer. Journal of ethnopharmacology. 2000; 71 (3):457-63. [22] Rafi MM, Vastano BC. Identification of a structure specific Bcl-2 phosphorylating homoisoflavone molecule from Vietnamese coriander (Polygonatum odoratum) that induces apoptosis and G2/M cell cycle arrest in breast cancer cell lines. Food chemistry. 2007; 104 (1):332-40. [23] Nambiar VS, Daniel M, Guin P. Characterization of polyphenols from coriander leaves (Coriandrum sativum), red amaranthus (A. paniculatus) and green amaranthus (A. frumentaceus) using paper chromatography and their health implications. Journal of Herbal Medicines and Toxicology. 2010; 4 (1):173-7. [24] Dapkevicius A, Venskutonis R, van Beek TA, Linssen JP. Antioxidant activity of extracts obtained by different isolation procedures from some aromatic herbs grown in Lithuania. Journal of the science of food and agriculture. 1998; 77 (1):140-6. [25] Wangensteen H, Samuelsen AB, Malterud KE. Antioxidant activity in extracts from coriander. Food chemistry. 2004; 88 (2):293-7. [26] Durak İ, Biri H, Ergüder İB, Devrim E, Şenocak Ç, Avcı A. Effects of garlic and black grape extracts on the activity of adenosine deaminase from cancerous and noncancerous human urinary bladder tissues. Medicinal Chemistry Research. 2007; 16 (6):259-65. [27] Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193 (1): 265-75. [28] Guisti G. Enzyme activities.1974; 1087-91 p. [29] Gansauge F, Ramadani M, Pressmar J, Gansauge S, Muehling B, Stecker K, et al. NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial. Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie. 2002; 386 (8): 570-4. [30] Colombo ML, Bosisio E. Pharmacological activities of Chelidonium majus L. (Papaveraceae). Pharmacological research: the official journal of the Italian Pharmacological Society. 1996; 33 (2):127-34. [31] Song JY, Yang HO, Pyo SN, Jung IS, Yi SY, Yun YS. Immunomodulatory activity of protein-bound polysaccharide extracted from Chelidonium majus. Archives of pharmacal research. 2002; 25 (2):158-64. [32] Kulp M, Bragina O. Capillary electrophoretic study of the synergistic biological effects of alkaloids from Chelidonium majus L. in normal and cancer cells. Analytical and bioanalytical chemistry. 2013; 405 (10):3391-7. [33] Namuslu M, Kocaoglu H, Celik HT, Avci A, Devrim E, Genc Y, et al. Effects of aqueous soybean, mistletoe and red clover extracts on activities of adenosine deaminase and xanthine oxidase enzyme. Bratislavske lekarske listy. 2014; 115 (6):367-71. [34] Jarred RA, Keikha M, Dowling C, McPherson SJ, Clare AM, Husband AJ, et al. Induction of apoptosis in low to moderate-grade human prostate carcinoma by red clover-derived dietary isoflavones. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2002; 11 (12):1689-96. [35] Lam AN, Demasi M, James MJ, Husband AJ, Walker C. Effect of red clover isoflavones on cox-2 activity in murine and human monocyte/macrophage cells. Nutrition and cancer. 2004; 49 (1):89-93. [36] Chen J, Wang L, Thompson LU. Flaxseed and its components reduce metastasis after surgical excision of solid human breast tumor in nude mice. Cancer letters. 2006; 234 (2):168-75. [37] Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, Ruffin MTt, et al. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer epidemiology, biomarkers & preventio: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2008; 17 (12):3577-87. [38] Azrad M, Vollmer RT, Madden J, Dewhirst M, Polascik TJ, Snyder DC, et al. Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer. Journal of medicinal food. 2013; 16 (4):357-60. [39] Chen J, Stavro PM, Thompson LU. Dietary flaxseed inhibits human breast cancer growth and metastasis and downregulates expression of insulin-like growth factor and epidermal growth factor receptor. Nutrition and cancer. 2002; 43 (2):187-92. [40] Kampman E, Vrieling A, van Duijnhoven FJ, Winkels RM. Impact of Diet, Body Mass Index, and Physical Activity on Cancer Survival. Current nutrition reports. 2012; 1: 30-6.