Hardaliyenin HT-29, DU-145, HeLa Kanser Hücreleri ve CF-1 (Fare Embriyonik Fibroblast) Hücresi FoxM1 Gen Expresyon Seviyelerine Etkisi

Yıl 2017, Cilt: 15 Sayı: 2, 119 - 123, 11.08.2017

Özge Kahraman Ilıkkan

https://doi.org/10.24323/akademik-gida.333633

Cited By: 2

Öz

Kemoterapötik ajanlar hem kanser hücrelerini hem de sağlıklı hücreleri etkilemektedir
bu nedenle alternatif terapötik ajanlar veya hedefler kanser tedavisinin
kilometre taşı olmuştur. Forkhead box M1 (FoxM1) transkripsiyonel regülatördür
ve kanser hücrelerinde daha fazla eksprese olması nedeniyle yeni kanser terapi
hedefi olmuştur. Fox M1 inhibitörleri, kanser gelişimini engelleyen potansiyel terapötik
ajanlardır. Bu nedenle, çalışmada, Hardaliye’nin kanser hücreleri ve sağlıklı
hücre hattı üzerine etkisi MTT yöntemiyle öncelikle belirlenmiş ve sonrasında,
FoxM1 gen ekspresyon seviyeleri tayin edilmiştir. Hardaliye, özellikle on ve
yirmi-kat seyreltildiğinde bütün kanser hücrelerinin yüzde canlılığını düşürmüş
ancak sağlıklı hücreleri etkilememiştir. FoxM1 seviyeleri sağlıklı hücre
hatlarında istatistiksel olarak değişmezken, kanser hücrelerinde özellikle
HT-29 hücrelerinde epeyce düşmüştür.

Anahtar Kelimeler

FoxM1, qRT-PCR, Kanser hücre hatları, CF-1, Gen ekspresyonu

Effect of Hardaliye on FoxM1 Gene Expression Level of HT-29, DU-145, HeLa Cancer Cells and CF-1 (Mouse Embryonic Fibroblast)

Öz

Chemotherapeutic agents may influence both cancer cells and healthy
cells, therefore alternative therapeutic agents or targets have become a milestone of cancer cure. Forkhead box M1 (FoxM1)
is a transcriptional regulator and a novel cancer therapy target as
overexpressed in cancer cells, and its inhibitors are considered as potential
therapeutic agents to halt cancer progression. Therefore, in this study, the
effect of “Hardaliye” on cancer cells and
a healthy cell line was primarily investigated
by MTT (3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide) and later
on, FoxM1 gene expression levels were determined. Hardaliye, especially when diluted ten and twenty-fold, decreased
viability percentage of all cancer cells and did not affect healthy cells.
FoxM1 levels of cancer cells drastically decreased especially in HT-29 cells
while did not statistically change their levels in the healthy cell line.

Anahtar Kelimeler

FoxM1, qRT-PCR, Cancer cell lines, CF-1, Gene expression

Kaynakça

• [1] Wang, Z., Ahmad, A., Li, Y., Banerjee, S., Kong, D., Sarkar, F.H., 2010. Forkhead box M1 transcription factor: a novel target for cancer therapy. Cancer Treatment Reviews 36(2): 151-156.
• [2] Laoukili, J., Stahl, M., Medema, R.H., 2007. FoxM1: at the crossroads of ageing and cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 1775(1): 92-102.
• [3] Koo, C.Y., Muir, K.W., Lam, E.W.F., 2012. FOXM1: From cancer initiation to progression and treatment. Biochimica et Biophysica (BBA)-Gene Regulatory Mechanisms 1819(1): 28-37.
• [4] Myatt, S.S., Lam, E.W.F., 2007. The emerging roles of forkhead box (Fox) proteins in cancer. Nature Reviews Cancer 7(11): 847-859.
• [5] Nogueira, V., Hay, N., 2013. Molecular pathways: reactive oxygen species homeostasis in cancer cells and implications for cancer therapy. Clinical Cancer Research 19(16): 4309-4314.
• [6] Raychaudhuri, P., Park, H.J., 2011. FoxM1: a master regulator of tumor metastasis. Cancer Research 71(13): 4329-4333.
• [7] Halasi, M., Pandit, B., Wang, M., Nogueira, V., Hay, N., Gartel, A.L., 2013. Combination of oxidative stress and FOXM1 inhibitors induces apoptosis in cancer cells and inhibits xenograft tumor growth. The American Journal of Pathology 183(1): 257-265.
• [8] Kahraman, O., Doğanlar, O., Doğanlar, Z.B., Altınoluk, P., Soykan Kırbaş, A., 2015. Anti-Proliferative effect of the Hardaliye on HT-29 cell line (human colon cancer): phenolic and element content by LC MS/MS and ICP-MS, apoptosis and antioxidant related gene expressions by RT-qPCR. IV. International Molecular Biology Congress, November 27-29, 2015, Ankara, Turkey.
• [9] Amoutzopoulos, B., Löker, G.B., Samur, G., Çevikkalp, S.A., Yaman, M., Köse, T., Pelvan E., 2013. Effects of a traditional fermented grape‐based drink ‘hardaliye’ on antioxidant status of healthy adults: a randomized controlled clinical trial. Journal of Science of Food and Agriculture 93(14): 3604-3610.
• [10] Abaza, M.S.I., Orabi, K.Y., Al-Quattan, E., Raja’a, J., 2015. Growth inhibitory and chemo-sensitization effects of naringenin, a natural flavanone purified from Thymus vulgaris, on human breast and colorectal cancer. Cancer Cell International 15(46):1-19.
• [11] Jiang, L., Cao, X.C., Cao, J.G., Liu, F., Quan, M.F., Sheng, X.F., Ren, K.Q., 2013. Casticin induces ovarian cancer cell apoptosis by repressing FoxM1 through the activation of FOXO3a. Oncology letters 5(5): 1605-1610.
• [12] Livak, K.J., Schmittgen, T.D., 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25(4): 402-408.
• [13] Rosa, L.S., Silva, N.J.A., Soares, N.C.P., Monteiro, M.C., Teodoro, A.J., 2016. Anticancer properties of phenolic acids in colon cancer - A review. Journal of Nutrition & Food Sciences 6:468.
• [14] Zhao, B., Hu, M., 2013. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells. Oncology letters 6(6):1749-1755.
• [15] Sun, G., Zhang, S., Xie, Y., Zhang, Z., Zhao, W., 2016. Gallic acid as a selective anticancer agent that induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells. Oncology Letters 11(1):150-158.
• [16] Faried, A., Kurnia, D., Faried, L.S., Usman, N., Miyazaki, T., Kato, H., Kuwano, H., 2007. Anticancer effects of gallic acid isolated from Indonesian herbal medicine, Phaleria macrocarpa (Scheff.) Boerl, on human cancer cell lines. International Journal of Oncology 30(3):605-614.
• [17] Liang, C.Z., Zhang, X., Li, H., Tao, Y.Q., Tao, L.J., Yang, Z.R., Zhou, X.P., Shi, Z.L., Tao, H.M., 2012. Gallic acid induces the apoptosis of human osteosarcoma cells in vitro and in vivo via the regulation of mitogen-activated protein kinase pathways. Cancer Biotherapy and Radiopharmaceuticals 27(10):701-710.
• [18] Carter, L.G., D'Orazio, J.A., Pearson, K.J., 2014. Resveratrol and cancer: focus on in vivo evidence. Endocrine-Related Cancer 21(3): 209-225.
• [19] Newick, K., Cunniff, B., Preston, K., Held, P., Arbiser, J., Pass, H., Heintz, N., 2012. Peroxiredoxin 3 is a redox-dependent target of thiostrepton in malignant mesothelioma cells. PLoS ONE 7(6): e39404.
• [20] Park, H.J., Carr, J.R., Wang, Z., Nogueira, V., Hay, N., Tyner, A.L., Raychaudhuri, P., 2009. FoxM1, a critical regulator of oxidative stress during oncogenesis. The EMBO Journal 28(19): 2908-2912.