6-SHOGAOL, 6-GİNGEROL VE KURKUMİN’ İN A549 HÜCRELERİNDE CANLILIK ÜZERİNE ETKİLERİ

Year 2017, Volume: 26 Issue: 1, 24 - 28, 01.03.2017

Eren Demirpolat Mükerrem Betül Yerer Aycan

Abstract

Çalışmamızda A549 küçük hücreli olmayan akciğer kanseri hücrelerinde Zingiber officinale’de bulunan 6- gingerol ile 6-shogaolün antikanser etkileri canlılık üzerinden araştırılmıştır. Deneyler hem IL-1β’ ya maruz
kalan hem de maruz kalmayan hücrelerde yürütüldü.
Curcuma longa’ da bulunan kurkumin bilinen doğal bir
antikanser molekül olduğundan çalışmada pozitif kontrol olarak kullanıldı ve kurkumine yapıca benzer olan 6
-gingerol ile 6-shogaolün canlılık üzerine olan etkileri
kurkuminle kıyaslandı. MTT (3-(4,5-dimetiltiazol-2-il)- 2,5-difenil tetrazolyum bromür) deneyleri öncelikle 6- gingerol ve 6-shogaolün birbirini logaritmik şekilde
seyreden konsantrasyonlarında yapıldı. Daha sonra etki
görülen konsantrasyon aralığını kapsayacak şekilde IC50 değerini belirlemek için deneyler tekrarlandı. Sonuç
olarak 6-shogaolun 24 sa IC50 değeri IL-β’ ya maruz kalmayan hücrelerde 62,5 μM; IL-β’ ya maruz kalan hücrelerde ise 63,2 μM olarak bulundu. Kurkumin 100 μM
konsantrasyonu ile kıyaslandığında 6-shogaolün daha
önceden antikanser özelliği gösterilmiş olan kurkumin
kadar etkin olduğu görülürken; 6-gingerol için canlılığı
azaltıcı yönde bir bulguya rastlanmadı. 6-shogaol’ un
canlılığı azaltıcı etkisinin altında yatan moleküler
mekanizmalar araştırılmaya değerdir.

Keywords

A549, 6-gingerol, 6-shogaol, kurkumin, IL-1β

Effects of 6-Shogaol, 6-Gingerol and Curcumin on Cell Viability in A549 Cancer Cell Line

Abstract

In our study we investigated anticancer effects of 6- gingerol and 6-shogaol from Zingiber officinale. Anticancer effect was monitored by using cell viability assay.
Experiments are performed on both A549 cells that are
incubated with IL-1β (interleukin 1 β) and cells which
are not incubated with it. Curcumin from Curcuma
longa, a natural compound that is known for its anticancer effect, is used as a positive control and effects of 6- gingerol and 6-shogaol are compared with it. MTT (3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide) assay was performed for wide range concentrations. Concentration changes were 10 fold. To obtain
IC50 values of 6-shogol and 6-gingerol, MTT assays were
performed again, using the previous concentrations but
in a narrower range.According to the assays 6-shogaol’s
24 h IC50 determined as 62,5 μM for A549 cells which
were not incubated with IL-1β and 63,2 μM for the cells
which were exposed to IL-1β. 6-shogaol’s cytotoxic effect was as much as curcumin which is a known natural
anticancer molecule, while 6-gingerol did not show any
effect towards decreasing the cell viability. Mechanisms
which underly 6-shogoal’s cytotoxic effect are worth for
further investigation.

Keywords

A549, 6-gingerol, 6-shogaol, curcumin, IL- 1β

References

• Rang H P, Dale M M, Ritter J M, Flower R J. Drugs used for the treatment of infections, cancer and immunological disorders, Anticancer drugs, In: Rang and Dale’s Pharmacology (7th ed), Elsevier Churchill Livingstone, Spain, 2012: p 673-687.
• IARC Press Release, Latest world cancer statistics, World Health Organization Report No223, France, 2013: p 1-3.
• Kayaalp O. Kanser Kemoterapisinin Esasları ve Antineoplastik İlaçlar, In: Rasyonel Tedavi Yönünden Tıbbi Farmakoloji (12. baskı), Pelikan Yayıncılık, Ankara, 2009: p 315-342.
• Celis E J. Cytotoxicity and Cell Growth Assays. In: Cell Biology A Laboratory Handbook (3rd ed), Elsevier Academic Press, 2006: s 315-324.
• Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65(1-2): 55-63.
• Riss T L, Moravec R A, Niles A L, et al. Cell Viability Assays. In: Assay Guidance Manual. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences 2013; s e- kitap.
• Koeberle A, Northoff H, Werz O. Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1. Mol Cancer Ther 2009; 8(8): 2348-2355.
• Gruenwald J, Brendler T, Jaenicke C, et al. PDR for Herbal Medicines. E-PDR Medical Economics Company 2000: p 339-342.
• Shukla Y, Singh M. Cancer preventive properties of ginger: A brief review. Food Chem Toxicol 2007; 45: 683-690.
• Koeberlea A, Haberlb E-M, Rossic A, et al. Discovery of benzo[g]indol-3-carboxylates as potent inhibitors of microsomal prostaglandin E2 synthase-1. Bioorg Med Chem Lett 2009; 17(23): 7924-7932
• Bia X, Xiaa X, Mou T, et al. Anti-tumor activity of three ginsenoside derivatives in lung cancer is associated with Wnt/β-catenin signaling inhibition. Eur J Pharmacol 2014: 742; 145-152.
• Shiroa T, Takahashia H, Kakiguchi K, et al. Synthesis and SAR study of imidazoquinolines as a novel structural class of microsomal prostaglandin E2 synthase-1 inhibitors. Bioorg Med Chem Lett 2012; 22(1): 285-288.
• Li Y Q, Yin S M, Nie D N, et al. MK886 inhibits the proliferation of HL-60 leukemia cells by suppressing the expression of mPGES-1 and reducing prostaglandin E2 synthesis. Int J Hematol 2011; 94: 472 -478.
• Staffan T, Jakobsson P J. Coordinate up- and down- regulation of glutathione dependent prostaglandin E synthase and cyclooxygenase-2 in A549 cells Inhibition by NS-398 and leukotriene C. Eur J Biochem 2000; 267: 6428-6434.
• Jakobsson P J, Thore´N S, Morgenstern R, et al. Identification of human prostaglandin E synthase: A microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Biochemistry 1999; 96: 7220-7225.
• Price P, McMillan T J. Use of the tetrazolium assay in measuring the response of human tumor cells to ionizing radiation. Cancer Research 1990; 50: 1392-1396
• American botanical council. Therapeutic Guide To Herbal Medicines, Commission E Monographs 1999; p: Turmeric root chapter.
• Chen Q, Wang Y, Xu K, et al. Curcumin induces apoptosis in human lung adenocarcinoma A549 cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Oncol Rep 2010; 23(2): 397-403.
• Yin H, Guo R, Xu Y, et al. Synergistic antitumor efficiency of docetaxel and curcumin against lung cancer. Acta Biochim Biophys Sin 2012; 44: 147– 153.
• Zhu y, Warin R F, Soroka D N, et al. Metabolites of ginger component [6]-shogaol remain bioactive in cancer cells and have low toxicity in normal cells: chemical synthesis and biological evaluation. Plos One 2013; 8 (1): 1-13.
• Ishiguroa K, Andob T, Maedab O, et al. Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms. Biochem Bioph Res Co 2007 ; 362 (1): 218-223.
• H Ling, H Yang, S-H Tan, et al. 6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-kB activation. Brit J Pharmacol 2010; 161: 1763-1777.
• Hsy Y L, Hung J Y, Tsai Y M, et al. 6‑Shogaol, an active constituent of dietary ginger, impairs cancer development and lung metastasis by inhibiting the secretion of cc-chemokine ligand 2 (ccl2) in tumor-associated dendritic cells. J Agric Food Chem 2015: 63; 1730-1738.