APIGENIN – ANTIMUTAGENNÍ ÚČINKY A PREVENCE RAKOVINY

APIGENIN – ANTIMUTAGENIC EFFECTS AND CANCER PREVENTION

Zdeňka Navrátilová1, Jiří Patočka2
1Přírodovědecká fakulta Univerzity Karlovy v Praze, katedra botaniky; 2Jihočeská univerzita v Českých Budějovicích, Zdravotně sociální fakulta, katedra radiologie a toxikologie

Korespondenční autor: Zdeňka Navrátilová (navratil@natur.cuni.cz)

ISSN 1804-7858 (On-line)

Full verze:
Full version

Submitted:12. 3. 2012
Accepted: 29. 5. 2012
Published online: 29. 6. 2012

Summary

Cancer is one of main causes of endangering the human life, which is every year documented by about seven million deaths worldwide. The occurrence of cancer is, however, dramatically different in different regions and populations, particularly between developing and developed countries. Epidemiological findings indicate that the occurrence of cancer is affected by many environmental factors including the food and that diseases can be prevented to a considerable extent. Approaches to the cancer prevention include two overlapping strategies: chemoprevention or prevention of cancer by diet. Chemoprevention is focused on prevention or disruption of the initiating stage of carcinogenesis or discontinuation of the carcinogenesis progression with the help of natural food components or by administering pharmacologically effective substances. The cancer prevention with food may be particularly achieved by essential enhancement of the intake of the fruits and vegetables. A considerable attention was paid to the identification of plant substances in the food, which could be used as suitable chemoprotectants. One of these natural substances searching for their successful use is a flavone apigenin. This substance is comprised in considerable amounts in usual fruits and vegetables, including parsley, onion, orange, tea, chamomile, wheat germs and some types of spices. Apigenin was demonstrated to have considerable anti-inflammatory, anti-oxidative and anti-cancer effects. Over recent years, a considerable progress was achieved in the study of biological effects of apigenin at cellular and molecular levels. The work presented here deals with chemoprotective effects of apigenin at an organ-specific level and evaluates its restriction and potential for the development of a new medicine for the cancer prevention.

Keywords: flavonoids – apigenin – cancer prevention – chemoprevention – food

Souhrn

Rakovina je jednou z hlavních příčin ohrožení života, což dokládá každým rokem přibližně 7 milionů úmrtí na celém světě. Výskyt rakoviny je však dramaticky odlišný v různých regionech a v různých populacích, zvláště mezi rozvojovými a rozvinutými zeměmi. Epidemiologické nálezy ukazují, že výskyt rakoviny je ovlivněn mnoha faktory životního prostředí včetně stravy a že nemoci lze do značné míry předcházet. Přístupy k prevenci rakoviny zahrnují dvě překrývající se strategie: chemoprevence nebo prevence rakoviny dietou. Chemoprevence se zaměřuje na prevenci či narušení zahajovací fáze karcinogeneze nebo zastavení progrese karcinogeneze pomocí přirozeně se vyskytujících složek potravy nebo podávání farmakologicky účinné látky. Prevence rakoviny pomocí stravy může být dosaženo zejména podstatným zvýšením spotřeby ovoce a zeleniny. Značná pozornost byla věnována identifikaci rostlinných látek ve stravě, které by mohly být využity jako vhodná chemoprotektiva. Jednou z těchto přirozeně se vyskytujících látek, která hledá uplatnění, je flavon apigenin. Tato sloučenina je ve značném množství přítomná v běžném ovoci a zelenině, včetně petržele, cibule, pomerančů, čaje, heřmánku, pšeničných klíčků a některých druhů koření. Bylo prokázáno, že apigenin má významné protizánětlivé, antioxidační a protinádorové účinky. V posledních několika letech došlo k významnému pokroku při studiu biologických účinků apigeninu na buněčné a molekulární úrovni. Tato práce se zabývá chemoprotektivními účinky apigeninu na orgánově specifické úrovni a hodnotí jeho omezení a jeho potenciál pro vývoj nového léčiva pro prevenci rakoviny.

Klíčová slova: flavonoidy – apigenin – prevence rakoviny – chemoprevence – strava

Literatura

  1. Alberts B, Bray D, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2005). Základy buněčné biologie. Úvod do molekulární biologie buňky. Espero Publishing Ústí nad Labem. 740 p.
  2. Amsterdam JD, Li Y, Soeller I, Rockwell K, Mao JJ, Shults J (2009). A randomized, double-blind, placebo-controlled trial of oral Matricaria recutita (chamomile) extract therapy for generalized anxiety disorder. J Clin Psychopharmacol. 29/4: 378–382.
  3. Andersen OM, Markham KR (eds.) (2006). Flavonoids. Chemistry, Biochemistry and Applications. CRC Press, Taylor & Francis Group. 1197 p.
  4. Birt DF, Walker B, Tibbels MG, Bresnick E (1986). Anti-mutagenesis and anti-promotion by apigenin, robinetin and indole-3-carbinol. Carcinogenesis. 7/6: 959–963.
  5. Birt DF, Mitchell D, Gold B, Pour P, Pinch HC (1997). Inhibition of ultraviolet light induced skin carcinogenesis in SKH-1 mice by apigenin, a plant flavonoid. Anticancer Res. 17/1A: 85–91.
  6. Bruneton J (1999). Pharmacognosy. Phytochemistry. Medicinal Plants. 2nd ed. Intercept Ltd, Londres, Paris, New York. 1119 p.
  7. Buer CS, Imin N, Djordjevic MA (2010). Flavonoids: New Roles for Old Molecules. J Integr Plant Biol. 52/1: 98–111.
  8. Caltagirone S, Rossi C, Poggi A, Ranelletti FO, Natali PG, Brunetti M, Aiello FB, Piantelli M (2000). Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer. 87/4: 595–600.
  9. Campbell EL, Chebib M, Johnston GA (2004). The dietary flavonoids apigenin and (-)-epigallocatechin gallate enhance the positive modulation by diazepam of the activation by GABA of recombinant GABAA receptors. Biochem Pharmacol. 68/8: 1631–1638.
  10. Cermak R (2008). Effect of dietary flavonoids on pathways involved in drug metabolism. Expert Opin Drug Metab Toxicol. 4/1: 17–35.
  11. Clere N, Faure S, Martinez MC, Andriantsitohaina R (2011). Anticancer properties of flavonoids: roles in various stages of carcinogenesis. Cardiovasc Hematol Agents Med Chem. 9/2: 62–77.
  12. Czyz J, Madeja Z, Irmer U, Korohoda W, Hülser DF (2005). Flavonoid apigenin inhibits motility and invasiveness of carcinoma cells in vitro. Int J Cancer. 114/1: 12–18.
  13. Černá M (1996). Jíte rádi flavonoidy? Vesmír 75/6: 304.
  14. EU Initiative (2012). EU allocates School Fruit Scheme funds. [online]. [cit. 10–03–2012]. Dostupné z: http://www.fruitnet.com/content.aspx?….
  15. Franzen CA, Amargo E, Todorović V, Desai BV, Huda S, Mirzoeva S, Chiu K, Grzybowski BA, Chew TL, Green KJ, Pelling JC (2009). The chemopreventive bioflavonoid apigenin inhibits prostate cancer cell motility through the focal adhesion kinase/Src signaling mechanism. Cancer Prev Res (Phila). 2/9: 830–841.
  16. Gravitz L (2011). Chemoprevention: First line of defence. Nature. 471/7339: S5–S7.
  17. Gray GE, Pike MC, Henderson BE (1979). Breast-cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices. Br J Cancer. 39/1: 1–7.
  18. Grotewold E (ed.) (2006). The Science of Flavonoids. Springer NY, USA. 273 p.
  19. Hampl R, Lapčík O (1996). Jíte rádi flavonoidy? Vesmír 75/3: 125.
  20. Han EK, McGonigal T (2007). Role of focal adhesion kinase in human cancer: a potential target for drug discovery. Anticancer Agents Med Chem. 7/6: 681–684.
  21. Hanrahan JR, Chebib M, Johnston GAR (2011). Flavonoid modulation of GABAA receptors. Br J Pharmacol. 163/2: 234–245.
  22. Henning SM, Wang P, Heber D (2011). Chemopreventive effects of tea in prostate cancer: green tea versus black tea. Mol Nutr Food Res. 55/6: 905–920.
  23. Chow HH, Hakim IA (2011). Pharmacokinetic and chemoprevention studies on tea in humans. Pharmacol Res. 64/2: 105–112.
  24. Johnson IT (2007). Phytochemicals and cancer. Proc Nutr Soc. 66/2: 207–215.
  25. Kirchheiner J, Brockmöller J (2005). Clinical consequences of cytochrome P450 2C9 polymorphisms. Clin Pharmacol Ther. 77/1: 1–16.
  26. Kontou N, Psaltopoulou T, Panagiotakos D, Dimopoulos MA, Linos A (2011). The mediterranean diet in cancer prevention: a review. J Med Food. 14/10: 1065–1078.
  27. Kumar S, Sharma A (2006). Apigenin: The Anxiolytic Constituent of Turnera aphrodisiaca. Pharm Biol. 44/2: 84–90.
  28. Kuo ML, Lee KC, Lin JK (1992). Genotoxicities of nitropyrenes and their modulation by apigenin, tannic acid, ellagic acid and indole-3-carbinol in the Salmonella and CHO systems. Mutat Res. 270/2: 87–95.
  29. Lepley DM, Pelling JC (1997). Induction of p21/WAF1 and G1 cell-cycle arrest by the chemopreventive agent apigenin. Mol Carcinog. 19/2: 74–82.
  30. Liang YC, Huang YT, Tsai SH, Lin-Shiau SY, Chen CF, Lin JK (1999). Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages. Carcinogenesis. 20/10: 1945–1952.
  31. Liu RH (2004). Potential Synergy of Phytochemicals in Cancer Prevention: Mechanism of Action. J Nutr. 134/12 Suppl.: 3479S–3485S.
  32. Long X, Fan M, Bigsby RM, Nephew KP (2008). Apigenin inhibits antiestrogen-resistant breast cancer cell growth through estrogen receptor-alpha-dependent and estrogen receptor-alpha-independent mechanisms. Mol Cancer Ther. 7/7: 2096–2108.
  33. Lukast A, Hóvári J. (2000). Flavonoid aglycons in foods of plant origin I. Vegetables. Chem Food Sci. 29/4: 345–352.
  34. McKay DL, Blumberg JB (2006). A review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.). Phytother Res. 20/7: 519–530.
  35. Medina JH, Viola H, Wolfman C, Marder M, Wasowski C, Calvo D, Paladini AC (1997). Flavonoids: A New Family of Benzodiazepine Receptor Ligands. Neurochem Res. 22/4: 419–425.
  36. Nielsen SE, Young JF, Daneshvar B, Lauridsen ST, Knuthsen P, Sandstrom B, Dragsted LO (1999). Effect of parsley (Petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects. Br J Nutr. 81/6: 447–455.
  37. Nijveldt RJ, van Nood E, van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAM (2001). Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr. 74/4: 418–425.
  38. Patel D, Shukla S, Gupta S (2007). Apigenin and cancer chemoprevention: progress, potential and promise (review). Int J Oncol. 30/1: 233–245.
  39. Russo M, Tedesco I, Iacomino G, Palumbo R, Russo GL (2005). Dietary Phytochemicals in Chemoprevention of Cancer. Curr Med Chem – Immun Endoc Metab Agents. 5/1: 61–72.
  40. Shukla S, Gupta S (2010). Apigenin: a promising molecule for cancer prevention. Pharm Res. 27/6: 962–978.
  41. Schultz C, Meier M, Schmid HP (2011). Nutrition, dietary supplements and adenocarcinoma of the prostate. Maturitas. 70/4: 339–342.
  42. Silvan S, Manoharan S, Baskaran N, Anusuya C, Karthikeyan S, Prabhakar MM (2011). Chemopreventive potential of apigenin in 7,12-dimethylbenz(a)an­thracene induced experimental oral carcinogenesis. Eur J Pharmacol. 670/2–3: 571–577.
  43. Singh P, Mishra SK, Noel S, Sharma S, Rath SK (2012). Acute exposure of apigenin induces hepatotoxicity in Swiss mice. PLoS One. 7/2: e31964.
  44. Takagaki N, Sowa Y, Oki T, Nakanishi R, Yogosawa S, Sakai T (2005). Apigenin induces cell cycle arrest and p21/WAF1 expression in a p53-independent pathway. Int J Oncol. 26/1: 185–189.
  45. Torkin R, Lavoie JF, Kaplan DR, Yeger H (2005). Induction of caspase-dependent, p53-mediated apoptosis by apigenin in human neuroblastoma. Mol Cancer Ther. 4/1: 1–11.
  46. Tsuji PA, Walle T (2008). Cytotoxic effects of the dietary flavones chrysin and apigenin in a normal trout liver cell line. Chem Biol Interact. 171/1: 37–44.
  47. van Nimwegen MJ, van de Water B (2007). Focal adhesion kinase: A potential target in cancer therapy. Biochem Pharmacol. 73/5: 597–609.
  48. Viola H, Wasowski C, Stein L, Wolfman C, Silveira R, Dajas F, Medina JH, Paladini AC (1995). Apigenin, a Component of Matricaria recutita Flowers, is a Central Benzodiazepine Receptors-Ligand with Anxiolytic Effects. Planta Med. 61/3: 213–216.
  49. Wang IK, Lin-Shiau SY, Lin J (1999). Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. Eur J Cancer. 35/10: 1517–1525.
  50. Wang W, Heideman L, Chung CS, Pelling JC, Koehler KJ, Birt DF (2000). Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines. Mol Carcinog. 28/2: 102–110.
  51. Way TD, Kao MC, Lin JK (2005). Degradation of HER2/neu by apigenin induces apoptosis through cytochrome c release and caspase-3 activation in HER2/neu-overexpressing breast cancer cells. FEBS Lett. 579/1: 145–152.
  52. Wei H, Tye L, Bresnick E, Birt DF (1990). Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice. Cancer Res. 50/3: 499–502.
  53. Winkel-Shirley B. (2001). Flavonoid Biosynthesis. A Colorful Model for Genetics, Biochemistry, Cell Biology, and Biotechnology. Plant Physiol. 126/2: 485–493.
  54. Yang CS, Landau, JM, Huang MT, Newmark HL (2001). Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu Rev Nutr. 21: 381–406.
  55. Zheng PW, Chiang LC, Lin CC (2005). Apigenin induced apoptosis through p53-dependent pathway in human cervical carcinoma cells. Life Sci. 76/12: 1367–1379.