Yıl: 2019 Cilt: 16 Sayı: 3 Sayfa Aralığı: 273 - 281 Metin Dili: İngilizce DOI: 10.4274/tjps.galenos.2018.27146 İndeks Tarihi: 25-08-2020

The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines

Öz:
Objectives: Natural products originating from plants have been used for many years in the treatment of various diseases, including cancer.Centaurea solstitialis subsp. solstitialis is used in Turkish folk medicine. This study was the first to determine the in vitro biological effects ofethanolic extract from the flowering parts of C. solstitialis L. subsp. solstitialis collected from Muğla Province.Materials and Methods: The cytotoxic effect was evaluated against Daudi, A549, and HeLa cancer cells and one normal BEAS-2B cell line usingthe MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- dipenyltetrazolium bromide) assay. Flow cytometric analysis and the caspase-3 activity assay wereperformed to detect apoptotic cell death. Angiogenic factor [vascular endothelial growth factor (VEGF)] secretion and the release of interleukin(IL)-1α, IL-6, and tumor necrosis factor (TNF)-α by cells treated with the extract were measured using enzyme-linked immunosorbent assay.Results: The extract exhibited cytotoxic effects against all the cancer cell lines used but HeLa and Daudi were the most sensitive cells, with IC50values of 63.18 µg/mL and 69.27 µg/mL, respectively. Selective cytotoxicity was observed between the HeLa and normal BEAS-2B cell lines. Theextract arrested the cell cycle at the S and G2 phases. In addition, apoptotic cell death was detected in HeLa and A549 cells. Moreover, the plantextract caused a significant decrease in VEGF secretion in A549 cells and a fluctuation in IL-1α, IL-6, and TNF-α secretion in A549 and Daudi cells.Conclusion: These observations suggest that the flowering parts of C. solstitialis may be a potential source in the development of natural drugs forthe treatment of cancer and modulation of cytokine secretion.
Anahtar Kelime:

İnsan Kanser Hücre Hatları Üzerinde Centaurea solstitialis Özütünün AntiKanser ve Anti-İnflamatuar Etkileri

Öz:
Amaç: Bitkilerden elde edilen doğal ürünler, kanser dahil çeşitli hastalıkların tedavisinde uzun yıllardır kullanılmaktadır. Centaurea solstitialis subsp. solstitialis’in Türk geleneksel tıbbında yeri olduğu bilinmektedir. Bu araştırma, Muğla ilinden toplanan C. solstitialis’in çiçekli kısımlarından elde edilen etanolik özütün in vitro biyolojik etkilerini belirleyen ilk çalışmadır. Gereç ve Yöntemler: Özütün Daudi, A549 ve HeLa kanser hücrelerine ve normal BEAS-2B hücre hattına karşı sitotoksik etkisi MTT (3-(4,5- dimetiltiyazol-2-il)-2,5-dipeniltetrazolyum bromür) testi ile belirlendi. Apoptotik hücre ölümü akış sitometri analizi ve kaspaz-3 aktivite deneyleriyle araştırıldı. Özüt ile muamele edilen hücreler tarafından üretilen anjiyojenik faktör [vasküler endotel büyüme faktörü (VEGF)] salınımı ve sitokinlerden interlökin (IL)-lα, IL-6 ve tümör nekroz faktör (TNF)-α’nın salınımı enzim bağlı immünosorbent deneyi testleriyle ölçüldü. Bulgular: Bitki özütü kullanılan tüm kanser hücre hatlarına karşı sitotoksik etki gösterirken, özüte karşı en duyarlı hücrelerin 63.18 µg/mL and 69.27 µg/mL olan IC50 değerleri ile sırasıyla HeLa ve Daudi hücreleri olduğu gözlendi. Seçici sitotoksisite HeLa ve normal BEAS-2B hücre hatları arasında tespit edildi. Bitki özütü S ve G2 fazlarında hücre döngüsü arrestine yol açtı. Buna ilave olarak, HeLa ve A549 hücrelerinde apoptotik hücre ölümü kaydedildi. Ayrıca bitki özütü A549 hücrelerinin VEGF salgılamasında anlamlı bir düşüşe yol açarken, A549 ile Daudi hücrelerinin IL-lα, IL-6 ve TNF-α salgılamasında önemli değişime neden oldu. Sonuç: Bu bulgular kanser tedavisi ve sitokin salgısının modülasyonunda gerekli olan doğal ilaçların geliştirilmesi için C. solstitialis’in çiçekli kısımlarının potansiyel bir kaynak olabileceğini göstermektedir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Raskin I, Ribnicky DM, Komarnytsky S, Ilic N, Poulev A, Borisjuk N, Brinker A, Moreno DA, Ripoll C, Yakoby N, O’Neal JM, Cornwell T, Pastor I, Fridlender B. Plants and human health in the twenty-first century. Trends Biotechnol. 2002;20:522-531.
  • 2. Unnati S, Ripal S, Sanjeev A, Niyati A. Novel anticancer agents from plant sources. Chin J Nat Med. 2013;11:16-23.
  • 3. Fan TP, Yeh JC, Leung KW, Yue PY, Wong RN. Angiogenesis: from plants to blood. Trends Pharmacol Sci. 2006;27:297-309.
  • 4. Tahergorabi Z, Khazaei M. A Review on Angiogenesis and Its Assays. Iran J Basic Med Sci. 2012;15:1110-1126.
  • 5. Schottenfeld D, Beebe-Dimmer J. Chronic Inflammation: A Common and Important Factor in the Pathogenesis of Neoplasia. CA Cancer J Clin. 2006;56:69-83.
  • . Oppenheim JJ, Murphy WJ, Chertox O, Schirrmacher V, Wang JM. Prospects for Cytokine and Chemokine Biotherapy. Clin Cancer Res.1997;3:2682-2686.
  • 7. Hollman, PC, Katan MB. Dietary Flavonoids: intake, health effects and bioavailability. Food Chem Toxicol.1999;37:937-942.
  • 8. Thun MJ, Henley, SJ, Patrono C. Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechanistic, Pharmacologic, and Clinical Issues. J Natl Cancer Inst. 2002;94:252-266.
  • 9. Güner A, Özhatay N, Ekim T, Başer K. Flora of Turkey and the East Aegean Islands. Vol 11. Edinburgh: Edinburgh University Press;2000.
  • 10. Altundag E, Ozturk M. Ethnomedicinal studies on the plant resources of east Anatolia. Procedia Soc Behav Sci. 2011;19:756-777.
  • 11. Honda G, Yeşilada E, Tabata M, Sezik E, Fujita T, Takeda Y, Takaishi Y, Tanaka T. Traditional medicine in Turkey VI. Folk medicine in West Anatolia: Afyon, Kütahya, Denizli, Muğla, Aydın provinces. J Ethnopharmacol. 1996;53:75-87.
  • 12. Sezik E, Yeşilada E, Honda G, Takaishi Y, Takeda Y, Tanaka T. Traditional medicine in Turkey X. Folk medicine in Central Anatolia. J Ethnopharmacol. 2001;75:95-115.
  • 13. Bulut G, Tuzlaci E. An ethnobotanical study of medicinal plants in Turgutlu (Manisa-Turkey). J Ethnopharmacol. 2013;149:633-647.
  • 14. Fujita T, Sezik E, Tabata M, Yeşilada E, Honda G, Takeda Y, Tanaka T, Takaishi Y. Traditional Medicine in Turkey VII.Folk Medicine in Middle and West Black Sea Regions. Econ Bot. 1995;49:406-422.
  • 15. Khammar A, Djeddi S. Pharmacological and Biological Properties of some Centaurea Species. Eur J Sci Res. 2012;84:398-416.
  • 16. Kaïj-a-Kamb M, Amoros M, Girre L. The chemistry and biological activities of the genus Centaurea. Pharm Acta Helv. 1992;67:178-188.
  • 17. Aktumsek A, Zengin G, Guler GO, Cakmak YS, Duran A. Screening for in vitro antioxidant properties and fatty acid profiles of five Centaurea L. species from Turkey flora. Food Chem Toxicol. 2011;49:2914-2920.
  • 18. Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival: Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods. 1986;89:271-277.
  • 19. Bradford, MM. A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Anal Biochem. 1976;72:248-254.
  • 20. Hengartner, MO. The biochemistry of apoptosis. Nature. 2000;407:770- 776.
  • 21. Chung AS, Ferrara N. Developmental and Pathological Angiogenesis. Annu Rev Cell Dev Biol. 2011;27:563-584 .
  • 22. Koyama S, Sato E, Tsukadaira A, Haniuda M, Numanami H, Kurai M, Nagai S, Izumi T. Vascular endothelial growth factor mRNA and protein expression in airway epithelial cell lines in vitro. Eur Respir J. 2002;20:1449-1456.
  • 23. Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer. 2004;4:11-22.
  • 24. World Health Organization. World health statistics 2017: monitoring health for the SDGs, Sustainable Development Goals. Geneva: World Health Organization; 2017.
  • 25. Cragg GM, Newman DJ. Natural products: A continuing source of novel drug leads. Biochim Biophys Acta. 2013;1830:3670-3695.
  • 26. Tekeli Y, Sezgin M, Aktümsek A. Antioxidant property of Centaurea solstitialis L. from Konya, Turkey. Asian J Chem. 2008;20:4831-4835.
  • 27. Özçelik B, Gürbüz I, Karaoglu T, Yeşilada E. Antiviral and antimicrobial activities of three sesquiterpene lactones from Centaurea solstitialis L. ssp. solstitialis. Microbiol Res. 2009;164:545-552.
  • 28. Akkol EK, Arif R, Ergun F, Yesilada E. Sesquiterpene lactones with antinociceptive and antipyretic activity from two Centaurea species. J Ethnopharmacol. 2009;122:210-215.
  • 29. Gürbüz İ, Yesilada E. Evaluation of the anti-ulcerogenic effect of sesquiterpene lactones from Centaurea solstitialis L. ssp. solstitialis by using various in vivo and biochemical techniques. J Ethnopharmacol. 2007;112:284-291.
  • 30. Erenler R, Sen O, Yaglioglu AS, Demirtas I. Bioactivity-Guided Isolation of Antiproliferative Sesquiterpene Lactones from Centaurea solstitialis L. ssp. solstitialis. Comb Chem High Throughput Screen. 2016;19:66-72.
  • 31. Tugba Artun F, Karagoz A, Ozcan G, Melikoglu G, Anil S, Kultur S, Sutlupinar N. In vitro anticancer and cytotoxic activities of some plant extracts on HeLa and Vero cell lines. J BUON. 2016;21:720-725.
  • 32. Astari KA, Erel ŞB, Köse FA, Köksal Ç, Karaalp C. Cytotoxic and Antibacterial Activities of Centaurea cadmea Boiss. Turk J Pharm Sci. 2014;11:101-106.
  • 33. Zater H, Huet J, Fontaine V, Benayache S, Stévigny C, Duez P, Benayache F. Chemical constituents, cytotoxic, antifungal and antimicrobial properties of Centaurea diluta Ait. subsp. algeriensis (Coss. & Dur.) Maire. Asian Pac J Trop Med. 2016;9:554-561.
  • 34. Ghantous A, Tayyoun AA, Lteif GA, Saliba NA, Gali-Muhtasib H, ElSabban M, Darwiche N. Purified Salograviolide A isolated from Centaurea ainetensis causes growth inhibition and apoptosis in neoplastic epidermal cells. Int J Oncol. 2008;32:841-849.
  • 35. El-Najjar N1, Dakdouki S, Darwiche N, El-Sabban M, Saliba NA, GaliMuhtasib H. Anti-colon cancer effects of Salograviolide A isolated from Centaurea ainetensis. Oncol Rep. 2008;19:897-904.
  • 36. Hanahan D, Weinberg RA. The Hallmarks of Cancer. Cell. 200;100:57-70.
  • 37. Plati J, Bucur O, Khosravi-Far R. Apoptotic cell signaling in cancer progression and therapy. Integr Biol (Camb). 2011;3:279-296.
  • 38. Deepa M, Sureshkumar T, Satheeshkumar PK, Priya S. Purified mulberry leaf lectin (MLL) induces apoptosis and cell cycle arrest in human breast cancer and colon cancer cells. Chem Biol Interact. 2012;200:38-44.
  • 39. Yırtıcı Ü, Göger F, Sarımahmut M, Ergene A. Cytotoxic and apoptotic effects of endemic Centaurea fenzlii Reichardt on the MCF-7 breast cancer cell line. Turk J Biol. 2017;41:370-377.
  • 40. Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6:99-104.
  • 41. Masoumi Moghaddam S, Amini A, Morris DL, Pourgholami MH. Significance of vascular endothelial growth factor in growth. Cancer Metastasis Rev. 2012;31:143-162.
  • 42. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357:539-545.
  • 43. Fernandes JV, Cobucci RN, Jatobá CA, Fernandes TA, de Azevedo JW, de Araújo JM. The Role of the Mediators of Inflammation in Cancer Development. Pathol Oncol Res. 2015;21:527-534.
  • 44. Talhouk RS, El-Jouni W, Baalbaki R, Gali-Muhtasib H, Kogan J, Talhouk SN. Anti-inflammatory bio-activities in water extract of Centaurea ainetensis. J Med Plant Res. 2008;2:24-33.
  • 45. Erel SB, Demir S, Nalbantsoy A, Ballar P, Khan S, Yavasoglu NU, Karaalp C. Bioactivity screening of five Centaurea species and in vivo antiinflammatory activity of C. athoa. Pharm Biol. 2014;52:775-781.
  • 46. Koca U, Süntar IP, Keles H, Yesilada E, Akkol EK. In vivo anti-inflammatory and wound healing activities of Centaurea iberica Trev.ex Spreng. J Ethnopharmacol. 2009;126:551-556.
APA Alper M, güneş h (2019). The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. , 273 - 281. 10.4274/tjps.galenos.2018.27146
Chicago Alper Mehlika,güneş hatice The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. (2019): 273 - 281. 10.4274/tjps.galenos.2018.27146
MLA Alper Mehlika,güneş hatice The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. , 2019, ss.273 - 281. 10.4274/tjps.galenos.2018.27146
AMA Alper M,güneş h The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. . 2019; 273 - 281. 10.4274/tjps.galenos.2018.27146
Vancouver Alper M,güneş h The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. . 2019; 273 - 281. 10.4274/tjps.galenos.2018.27146
IEEE Alper M,güneş h "The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines." , ss.273 - 281, 2019. 10.4274/tjps.galenos.2018.27146
ISNAD Alper, Mehlika - güneş, hatice. "The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines". (2019), 273-281. https://doi.org/10.4274/tjps.galenos.2018.27146
APA Alper M, güneş h (2019). The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. Turkish Journal of Pharmaceutical Sciences, 16(3), 273 - 281. 10.4274/tjps.galenos.2018.27146
Chicago Alper Mehlika,güneş hatice The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. Turkish Journal of Pharmaceutical Sciences 16, no.3 (2019): 273 - 281. 10.4274/tjps.galenos.2018.27146
MLA Alper Mehlika,güneş hatice The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. Turkish Journal of Pharmaceutical Sciences, vol.16, no.3, 2019, ss.273 - 281. 10.4274/tjps.galenos.2018.27146
AMA Alper M,güneş h The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. Turkish Journal of Pharmaceutical Sciences. 2019; 16(3): 273 - 281. 10.4274/tjps.galenos.2018.27146
Vancouver Alper M,güneş h The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines. Turkish Journal of Pharmaceutical Sciences. 2019; 16(3): 273 - 281. 10.4274/tjps.galenos.2018.27146
IEEE Alper M,güneş h "The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines." Turkish Journal of Pharmaceutical Sciences, 16, ss.273 - 281, 2019. 10.4274/tjps.galenos.2018.27146
ISNAD Alper, Mehlika - güneş, hatice. "The Anticancer and Anti-inflammatory Effects of Centaurea solstitialis Extract on Human Cancer Cell Lines". Turkish Journal of Pharmaceutical Sciences 16/3 (2019), 273-281. https://doi.org/10.4274/tjps.galenos.2018.27146