Differential antitumor effect of essential oils and their major components of Thymus broussonettii: relationship to cell cycle and apoptosis induction

• Autorzy: Jaafari A , Ait Mouse H. , Ait M'Bark L. , Tilaoui M. , Elhansali M. , Lepoivre M. , Aboufatima R. , Melhaoui A. , Chait A. , Zyad A.

Warianty tytułu

PL

Rozne dzialania przeciwnowotworowe olejkow eterycznych Thymus broussonettii. Zwiazek z cyklem komorkowym i indukcja apoptozy

• Języki publikacji: EN

Abstrakty

EN

Thymus broussonettii, a Moroccan endemic plant, exists in two chemotypes. The aim of our study is to compare the cytotoxic activity of their essential oils and major products as well as their effect on cell cycle and apoptosis induction. The chemical composition analysis of essential oils by GC-SM revealed that the lasts are rich and diverse and the major products of the chemotypes TbA and TbE are carvacrol and thymol, respectively. The in vitro cytotoxic effect study against five tumor cell lines shows that TbA essential oil, rich in carvacrol, has an important cytotoxic effect, higher than that of TbE, rich in thymol. This result is confirmed by comparing cytotoxic effect of carvacrol and thymol. Furthermore, TbA EO /carvacrol and TbE EO /thymol induce cell cycle arrest at S and G0/G1 phases, respectively. On the other hand, carvacrol, most cytotoxic in vitro, was studied for its effect on solid tumor in vivo and apoptosis-induction. Our results show that carvacrol, administred by gavage, has an important effect on solid tumor and induce apoptosis in P815 tumor cell line.

PL

Istnieją dwa chemotypy Thymus broussonettii, marokańskiej rośliny endemicznej. Celem pracy było porównanie działania cytotoksycznego ich olejków eterycznych i głównych związków, a także ich wpływu na cykl komórkowy i indukcję apoptozy. Analiza składu chemicznego olejków eterycznych dokonana za pomocą GC-MS dowiodła, że są one bogate i zróżnicowane, a głównymi składnikami chemotypów TbA i TbE są odpowiednio karwakrol i tymol. Analiza działania cytotoksycznego przeprowadzona na pięciu liniach komórek nowotworowych in vitro wykazała, że olejek eteryczny z TbA, bogaty w karwakrol, ma działanie cytotoksyczne, większe niż TbE, o dużej zawartości tymolu. Te wyniki zostały potwierdzone przez porównanie działania cytotoksycznego samego karwakrolu i tymolu. Co więcej, zarówno olejek eteryczny z TbA jak i karwakrol indukują hamowanie cyklu komórkowego w fazie S, natomiast olejek eteryczny TbE i tymol hamują rozwój komórek w fazie G0/G1. Z drugiej strony karwakrol, najbardziej cytotoksyczny in vitro, analizowano pod kątem działania na guz lity in vivo oraz indukcji apoptozy. Wyniki pokazują, że karwakrol podawany dożołądkowo ma istotny wpływ na rozwój guza litego i indukcję apoptozy w linii komórkowej guza P815.

Słowa kluczowe

EN

Morocco; Thymus broussonetii; endemic plant; medicinal plant; essential oil; carvacrol; thymol; antitumour effect; anticancer activity; cytotoxic activity; chemical composition; cell cycle; apoptosis; apoptosis induction; pharmacological research

• Wydawca: -
• Czasopismo: Herba Polonica
• Rocznik: 2009
• Tom: 55
• Numer: 2
• Opis fizyczny: p.36-50, fig.,ref.

Twórcy

autor

Jaafari A

• Sultan Moulay Slimane University, Box 523, Beni-Mellal, Morocco

autor

Ait Mouse H.

autor

Ait M'Bark L.

autor

Tilaoui M.

autor

Elhansali M.

autor

Lepoivre M.

autor

Aboufatima R.

autor

Melhaoui A.

autor

Chait A.

autor

Zyad A.

Bibliografia

• 1. Meister A, Bernhardt G, Christoffel V, Buschauer A. Antispasmodic activity of Thymus vulgaris extract on the isolated guinea-pig trachea: discrimination between drug and ethanol effects. Planta Med 1999; 65:512-16.
• 2. Essawi T, Srour M. Screening of some Palestinian medicinal plants for antibacterial activity. J Ethnopharmacol 2000; 70:343-9.
• 3. S oliman KM , Badeaa RI . Effect of oil extracted from some medicinal plants on different mycotoxigenic fungi. Food Chem Toxicol 2002; 40:1669-75.
• 4. M iura K, Kikuzaki H, Nakatani N. Antioxidant activity of chemical components from sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.) measured by the oil stability index method. J Agric Food Chemi 2002; 50:1851-4. 48A. Jaafari, H. Ait Mouse, L. Ait M’bark, M. Tilaoui, M. Elhansali, M. Lepoivre, R. Aboufatima, A. Melhaoui, A. Chait, A. Zyad
• 5. T epe B, Sokmen M, Akpulat HA, Daferera D, Polissiou M., Sokmen A. Antioxidative activity of the ssential oils of Thymus sipyleus subsp.sipyleus var. sipyleus and Thymus sipyleus subsp. sipyleus var. rosulans. J Food Engin 2005; 66:447-54.
• 6. S evtap Aydýna A, Basaranb A, Basarana N. The effects of thyme volatiles on the induction of DNA damage by the heterocyclic amine IQ and mitomycin C. Mutation Res 2005; 581:43-53.
• 7. I smaili H, Sosa S, Brkic D, Fkih-Tetouani S, Ilidrissi A, Touati D, Aquino R, Tubaro A. Topical anti-inflammatory activity of extracts and compounds from Thymus broussonettii. J Pharmac Pharmacol 2002; 54:1137-40.
• 8. E lhabazi K, Dicko A, Desor F, Dalal A, Younos C, Soulimani R. Preliminary study on immunological and behavioural effects of Thymus broussonetii Boiss., an endemic species in Morocco. J Ethnopharmacol 2006; 103:413-19.
• 9. M osmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxic assay. J. Immunol Met 1983; 65:55-63.
• 10. Y oshikawa T, Kokura S, Tainaka K, Naito Y, Kondo MA. Novel cancer therapy based on oxygen radicals. Cancer Res 1995; 55:1617-20.
• 11. R ichard H, Benjilali B, Banquour N, Baritaux O. Etude de diverses huiles essentielles de thym du Maroc. Lebensm Wiss Technol 1985; 18:105-10.
• 12. B enjilali B, Hammoumi M. Polymorphisme chimique des huiles essentielles de thym du Maroc. Science des aliments 1987; 7:77-91
• 13. Jaafari A, Ait Mouse H, Rakib E, Ait M’barek L, Tilaoui M, Benbakhta C, Boulli A, Abbad A, Zyad A. Chemical composition and antitumor activity of different wild varieties of Moroccan thyme. Brazilian J Pharmacogn 2007; 17:477-91.
• 14. S tahl-Biskup E. The chemical composition of Thymus oils: review of the literature 1960-1989. J Ess Oil Res 1991; 3:61-82.
• 15. R aal A, Paaver U, Arak E, Orav A. Content and composition of the essential oil of Thymus serpyllum L. growing wild in Estonia. Medicina (Kaunas) 2004; 40:795-800.
• 16. S eung-Joo Lee, Katumi U, Takayuki S, Kwang-Geun L. Identification of volatile components in basil (Ocimum basilicum L.) and thyme leaves (Thymus vulgaris L.) and their antioxidant properties. J Food Chem 2005; 91:131-7.
• 17. S chmidt A, Christina Bischof-Deichnik, Stahl-Biskup E. Essential oil polymorphism of Thymus praecox subsp. arcticus on the British Isles. Biochem Sys Ecol 2004; 4:409-21.
• 18. E cheverrigaray S, Agostini G, Atti-Serfini L, Paroul N, Pauletti GF, dos Santos AC. Correlation between the chemical and genetic relationships among commercial thyme cultivars. J Agric Food Chem 2001; 49:4220-3.
• 19. Hudaib M, Speroni E, Di Pietra AM, Cavrini V. GC/MS evaluation of thyme (Thymus vulgaris L.) oil composition and variations during the vegetative cycle. J Pharm Biomed Anal 2002; 29:691-700.
• 20. Hanci S, Sahin S, Yilmaz L. Isolation of volatile oil from thyme (Thymbra spicata) by steam distillation. Nahrung 2003; 47:252-5.
• 21. Dursun N, Liman N, Ozyazgan I, Gunes I, Saraymen R. Role of thymus oil in burn wound healing. Lett Appl Microbiol 1999; 29:130-5.
• 22. Youdim KA, Deans SG. Effect of thyme oil and thymol dietary supplementation on the antioxidant status and fatty acid composition of the ageing rat brain. Br J Nutr 2000; 83:87-93.
• 23. Lee KG, Shibamoto T. Determination of antioxidant potential of volatile extracts isolated from various herbs and spices. J Agric Food Chem 2002; 50:4947-52.
• 24. Stammati A, Bonsi P, Zucco F, Moezelaar H-L, Alakomi von Wright A. Toxicity of selected plant volatils in microbial and mammalian short-term. Food Chem Toxicol 1999; 37:813-23.
• 25. He L, Mo H, Hadisusilo S, Qureshi AA, Elson CE . Isoprenoids suppress the growth of murine B16 melanomas in vitro and in vivo. J Nutr 1997; 127:668-74.
• 26. T ansu Koparal A, Zeytinoglu M. Effects of Carvacrol on a Human Non-Small Cell Lung Cancer (NSCLC ) Cell Line, A549. Cytotechnology 2003; 43:149-54. Y oshikawa T, Kokura S, Tainaka K, Naito Y, Kondo MA. novel cancer therapy based on oxygen radicals. Cancer Res. 1995; 55: 1617-1620.
• 27. Karkabounas S, Kostoula OK, Daskalou T, Veltsistas P, Karamouzis M, Zelovitis I. et al. Anticarcinogenic and antiplatelet effects of carvacrol. Exp Oncol 2006; 28:121-5.
• 28. Zeytinoglu H, Incesu Z, Baser KH. Inhibition of DNA synthesis by carvacrol in mouse myoblast cells bearing a human N-RAS oncogene. Phytomedicine. 2003; 10:
• 29. Horvathova E, Turcaniova V, Slamenova D. Comparative study of DNA-damaging and DNA-protective effects of selected components of essential plant oils in human leukemic cells K562. Neoplasma 2007; 54:478-83.
• 30. E vrim I, Hulya Zeytinoglu H, Sezer O, Berrin A, Tuylu M, Kurkcuoglu Husnu et al. Genotoxicity and antigenotoxicity of Origanum oil and carvacrol evaluated by Ames Salmonella/microsomal test. Food Chem 2005; 93:551-6.
• 31. Jordheim, LP ., Guittet, O., Lepoivre, M., Galmarini, C.M. and Dumontet, C. Increased expression of the large subunit of ribonucleotide reductase is involved in resistance to gemcitabine in human mammary adenocarcinoma cells. Mol Cancer Ther. 2005; 4(8):1268-76.
• 32. Hotz MA, Gong J, Traganos F, Darzynkiewicz Z. Flow cytometric detection of apoptosis: Comparison of the assays of in situ DNA degradation and chromatin changes. Cytometry 1994; 15:237-44.
• 33. Benitez DA, Pozo-Guisado E, Alvarez-Barrientos A, Fernandez-Salguero PM, Castellón EA. Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines. J Androl 2007; 28:282-93.
• 34. S hishodia S, Sethi G, Ahn KS, Aggarwal BB. Guggulsterone inhibits tumor cell proliferation, induces Sphase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. Biochem Pharmacol 2007; 74:118-30.
• 35. Prasad S, Kaur J, Roy P, Kalra N, Shukla Y. Theaflavins induce G2/M arrest by modulating expression of p21waf1/cip1, cdc25C and cyclin B in human prostate carcinoma PC -3 cells. Life Sci 2007; 81:1323-31.
• 36. K ornblau SM . The role of apoptosis in the pathogenesis, prognosis, and therapy of hematologic malignancies. Leukemia. 1998; 12 (Suppl. 1):S4.
• 37. Bimczok D, Rau H, Sewekow E, Janczyk P, Souffrant WB, Rothkötter HJ. Influence of carvacrol on proliferation and survival of porcine lymphocytes and intestinal epithelial cells in vitro. Toxicol In Vitro 2008; 22:652-8.