Ana OBRADOVIC, Jovana ZIZIC, Nemanja TRISOVIC, Bojan BOZIC, Gordana USCUMLIC, Biljana BOZIC, Snezana MARKOVIC

Evaluation of antioxidative effects of twelve 3-substituted-5,5-diphenylhydantoins on human colon cancer cell line HCT-116

Antioxidant effects of twelve 3-substituted-5,5-diphenylhydantoins in concentrations of 0.01, 0.1, 1, 10, and 100 µM on human colon cancer cell line HCT-116 were determined 24 h after treatment. The concentrations of superoxide anion radical (O2.-), nitrites (NO2-), and total glutathione were determined spectrophotometrically. Results indicated that treatment with all compounds induced a decrease in O2.- and an increase in NO2- concentrations in HCT-116 cells. Treatment with all compounds resulted in an increase in glutathione, and this indicates changes in redox homeostasis. Based on the obtained results, the investigated hydantoins act as antioxidants because they decrease the production of superoxide anion radical and increase concentrations of glutathione, but they also induce an increase in nitrite production.

Anahtar Kelimeler:

Key words: Antioxidants, phenytoin derivatives, free radicals, redox homeostasis

Evaluation of antioxidative effects of twelve 3-substituted-5,5-diphenylhydantoins on human colon cancer cell line HCT-116

Keywords:

Key words: Antioxidants, phenytoin derivatives, free radicals, redox homeostasis,

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Addabbo F, Montagnani M, Goligorsky MS (2009). Mitochondria and reactive oxygen species. Hypertension 53: 885–892.
Auclair C, Voisin E (1985). Nitroblue tetrazolium reduction. In: Greenwald RA, editor. Handbook of Methods for Oxygen Radical Research. Boca Raton, FL, USA: CRC Press, Inc., pp. 123–132.
Baker MA, Cerniglia GJ, Zaman A (1990). Microtiter plate assay for the measurement of glutathione and glutathione disulfide in large numbers of biological samples. Anal Biochem 190: 360– 3
Basappa, Ananda Kumar CS, Nanjunda Swamy S, Sugahara K, Rangappa KS (2009). Anti-tumor and anti-angiogenic activity of novel hydantoin derivatives: inhibition of VEGF secretion in liver metastatic osteosarcoma cells. Bioorg Med Chem 17: 4928–4934.
Carmi C, Cavazzoni A, Zuliani V, Lodola A, Bordi F, Plazzi PV, Mor M (2006). 5-Benzylidene-hydantoins as new EGFR inhibitors with antiproliferative activity. Bioorg Med Chem Lett 16: 4021–4025.
Cavazzoni A, Alfieri RR, Carmi C, Zuliani V, Galetti M, Fumarola C, Frazzi R, Bonelli M, Bordi F, Lodola A et al. (2008). Dual mechanisms of action of the 5-benzylidene-hydantoin UPR1024 on lung cancer cell lines. Mol Cancer Ther 7: 361– 3
Chew E, Matthews CS, Zhang J, McCarroll AJ, Hagen T, Stevens FGM, Westwell AD, Bradshaw TD (2006). Antitumor quinols: role of glutathione in modulating quinol-induced apoptosis and identification of putative cellular protein targets. Biochem Biophys Res Comun 346: 242–251.
Cook T, Wang Z, Alber S, Liu K, Watkins SC, Vodovotz Y, Billiar TR, Blumberg D (2004). Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53. Cancer Res 64: 8015–8021.
Eckhardt S (2002). Recent progress in the development of anticancer agents . Curr Med Chem Anti-Cancer Agents 2: 419–439.
Fidler IJ (2002). Critical determinants of metastasis. Semin Cancer Biol 12: 89–96.
Griess P (1879). Bemerkungen zu der Abhandlung der HH. Weselsky und Benedikt “Ueber einige Azoverbindungen”. Ber Dtsch Chem Ges 12: 426–428 (in German).
Henderson BR, Fagotto F (2002). The ins and outs of APC and betacatenin nuclear transport. EMBO Rep 3: 834–839.
Kim PK, Zamora R, Petrosko P, Billiar TR (2001). The regulatory role of nitric oxide in apoptosis. Int Immunopharmacol 1: 1421–1441.
Kumar ACS, Kavitha CV, Vinaya K, Benaka PSB, Thimmegoweda NR, Chandrappa S, Raghavan SC, Rangappa KS (2009). Synthesis and in vitro cytotoxic evaluation of novel diazaspiro bicyclo hydantoin derivatives in human leukemia cells: a SAR study. Invest New Drug 27: 327–337.
Lee CW, Hong DH, Han SB, Jong SH, Kim HC, Fine RL, Lee SH, Kim HM (2002). A novel stereo-selective sulfonylurea, 1-[1-(4-aminobenzoyl)-2,3-dihydro-1H-indol-6-sulfonyl]4-phenyl-imidazolidin-2-one, has antitumor efficacy in in vitro and in vivo tumor models. Bio Pharmacol 64: 473–480.
Liu Q, Chan STF, Mahendran R (2003). Nitric oxide induces cyclooxygenase expression and inhibits cell growth in colon cancer cell lines. Carcinogenesis 24: 637–642.
Maguire JH, Murthy AR, Hall IH (1985). Hypolipidemic activity of antiepileptic 5-phenylhydantoins in mice. Eur J Pharmacol 117: 135–138.
Manda G, Nechifor MT, Neagu TM (2009). Reactive oxygen species, cancer and anti-cancer therapies. Curr Chem Biol 3: 342–366.
Peklak-Scott C, Smitherman PK, Townsend AJ, Morrow CS (2008).
The role of glutathione S-transferase P1-1 (GSTP1-1) in the cellular detoxification of cisplatin. Mol Cancer Ther 7: 3247– 32
Rigas B, Williams JL (2008). NO-donating NSAIDs and cancer: an overview with a note on whether NO is required for their action. Nitric Oxide 19: 199–204.
Trišović N, Božić B, Obradović A, Stefanović O, Marković S, Čomić Lj, Božić B, Ušćumlić G (2011). Structure-activity relationships of 3-substituted-5,5-diphenylhydantoins as potential antiproliferative and antimicrobial agents. J Serb Chem Soc 76: 1597–1606.
Valko M, Rhodes CJ, Mancol J, Izakovic M, Mazur M (2006). Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160: 1–40.
Wink DA, Vodovotz Y, Laval J, Laval F, Dewhirst MW, Mitchell JB (1998). The multifaceted roles of nitric oxide in cancer. Carcinogenesis 19: 711–721.
Yaari Y, Selzer ME, Pincus JH (1986). Phenytoin: mechanisms of its anticonvulsant action. Ann Neurol 20: 171–184.
Yang J, Li TZ, Xu GH, Luo BB, Chen YX, Zhang T (2013). Lowconcentration capsaicin promotes colorectal cancer metastasis by triggering ROS production and modulating Akt/mTOR and STAT-3 pathways. Neoplasma 60: 364–372.