Anti-Proliferative Effect of Melamine on Human Colon Adenocarcinoma Cells

Öz

Melamine is an organic chemical used primarily as a plastics stabilizer and fire retardant. Also, it was used to fraudulently elevate the protein content of animal feed and dairy products, which led to infant kidney diseases and pet deaths. In this study, melamine was studied for its effects on growth in the human colon adenocarcinoma cells (Caco-2). Different concentrations of medium-dissolved melamine were incubated for 24 h with Caco-2 cells and tested for its anti-proliferative potential using MTT assay. Half-maximal inhibitory concentration (IC₅₀) of melamine was calculated from dose-response curve and found to be 14636 µg/L in the cells. The results demonstrated that the dose dependent melamine decreased cell proliferation and direct anti-proliferative effect in Caco-2 cells. 

Anahtar Kelimeler

• Anti-proliferative,Caco-2,Melamine,MTT

Melaminin İnsan Kolon Adenokarsinom Hücreleri Üzerindeki Anti-Proliferatif Etkisi

Öz

Melamin, öncelikle plastik dengeleyici ve yangın geciktirici olarak kullanılan organik bir kimyasaldır. Hayvansal yem ve süt ürünlerinin protein içeriğini suni şekilde yükseltmek için kullanılmasıyla bebeklerde böbrek hastalıklarına ve hayvan ölümlerine yol açmıştır. Bu çalışmada, melaminin insan kolon adenokarsinom hücrelerinin (Caco-2) proliferasyonu üzerine etkileri araştırılmıştır. Farklı konsantrasyonlarda çözülmüş melamin Caco-2 hücreleri ile 24 saat inkübe edildi ve MTT testi kullanılarak anti-proliferatif potansiyeli test edildi. Melaminin yarı maksimal inhibisyon konsantrasyonu (IC₅₀), doz-cevap eğrisinden hesaplandı ve hücrelerde 14636 µg/L olarak bulundu. Sonuçlar doza bağımlı olarak melaminin Caco-2 hücrelerinin proliferasyonunu azalttığını ve Caco-2 hücrelerine karşı anti-proliferatif etkiye sahip olduğunu göstermiştir.

Anahtar Kelimeler

• Anti-proliferatif,Caco-2,Melamin,MTT

Kaynakça

1. Aslantürk ÖS. In Vitro Cytotoxicity and Cell Viability Assays: Principles, Advantages, and Disadvantages. In Genotoxicity-A Predictable Risk to Our Actual World. IntechOpen. 2017; DOI: 10.5772/intechopen.71923.
2. Bilir EK, Tutun H, Sevin S, Kısmalı G, Yarsan E. Cytotoxic Effects of Rhododendron ponticum L. Extract on Prostate Carcinoma and Adenocarcinoma Cell Line (DU145, PC3). Kafkas Univ Vet Fak Derg, 2018; 24(3): 451-457.
3. Chan EYY, Griffiths SM, Chan CW. Public-health risks of melamine in milk products Lancet, 2008; 372 (9648): 1444-1445
4. Choi L, Kwak MY, Kwak EH, Kim DH, Han EY, Roh T, Bae JY, Ahn IY, Kwon MJ, Jang DE, Lim SK, Kwack SJ, Han SY, Kang TS, Kim SH, Kim HS, Lee BM. Comparative nephrotoxicity induced by melamine, cyanuric acid, or a mixture of both chemicals in either Sprague-Dawley rats or renal cell lines. J Toxicol Environ Health A, 2010; 73(21-22): 1407-1419.
5. Florento L, Matias R, Tuaño E, Santiago K, dela Cruz F, Tuazon A. Comparison of cytotoxic activity of anticancer drugs against various human tumor cell lines using in vitro cell-based approach. Int J Biomed Sci, 2012; 8(1): 76.
6. Guan X, Deng Y. Melamine-associated urinary stone. Int J Surg, 2016; 36(d), 613-617.
7. Guo C, Yuan H, He Z. Melamine causes apoptosis of rat kidney epithelial cell line (NRK‐52e cells) via excessive intracellular ROS (reactive oxygen species) and the activation of p38 MAPK pathway. Cell Biol Int, 2012; 36(4): 383-389.
8. Han YG, Liu SC, Zhang T, Yang Z. Induction of apoptosis by melamine in differentiated PC12 cells. Cell Mol Neurobiol, 2011; 31(1): 65-71.

9. Hau AKC, Kwan TH, Li PKT. Melamine toxicity and the kidney. J Am Soc Nephrol, 2009; 20(2): 245-250
10. Hsieh TJ, Hsieh PC, Tsai YH, Wu CF, Liu CC, Lin MY, Wu MT. Melamine induces human renal proximal tubular cell injury via transforming growth factor-β and oxidative stress. Toxicol Sci, 2012; 130(1): 17-32.
11. Liu X, da Huang W, Wu KJ, Wu YN, Jia XW, Gong ZY. An evaluation of genotoxicity and cytotoxicity of melamine in combination with cyanuric acid at three mass ratios. Bio Environ Sci, 2014; 27(8): 641-645.
12. Mervin LH, Cao Q, Barrett IP, Firth MA, Murray D, McWilliams L, Haddrick M, Wigglesworth M, Engkvist O, Bender A. Understanding cytotoxicity and cytostaticity in a high-throughput screening collection. ACS Chem. Biol., 2016; 11(11): 3007-3023.
13. Radko L, Minta M, Stypula-Trebas S, Zmudzki J. Determination of melamine cytotoxicity. Bull Vet Inst Pulawy, 2010; 54: 223-228.
14. Skinner CG, Thomas JD, Osterloh JD. Melamine toxicity. J Med Toxicol, 2010; 6(1): 50-55.
15. Sun H, Wang K, Wei H, Li Z, Zhao H. Cytotoxicity, organ distribution and morphological effects of melamine and cyanuric acid in rats. Toxicol Mech Methods, 2016; 26(7): 501-510.
16. Ulukaya E, Ozdikicioglu F, Oral AY, Demirci M. The MTT assay yields a relatively lower result of growth inhibition than the ATP assay depending on the chemotherapeutic drugs tested. Toxicol in vitro, 2008; 22(1): 232-239.