Abstract
Gastric cancer is among the leading causes of cancer-related death, and the symptoms are commonly characterized in advanced stages. Histone acetylation is among the most important epigenetic alterations occurring during cancer development. In addition, reduced E-cadherin expression is a major contributor in the process of tumor cell invasion and metastasis. Oxamflatin is a histone deacetylase inhibitor that has been suggested as a promising anti-tumor agent; yet its effect on the viability and invasion of gastric tumor cells is unclear. We aimed to assess the impact of oxamflatin on the viability of gastric tumor cells and expression of E-cadherin as a marker of tumor invasion susceptibility. In this study, MKN-45 cells were treated with 1, 2.5 and 5 mM oxamflatin and followed by MTT assay after 24–48 h of incubation. To determine E-cadherin expression in treated cells, total RNA was extracted and reverse transcribed to complementary DNA, followed by quantitative real-time PCR. MTT results showed that the viability of MKN-45 cells declines with increasing concentrations of oxamflatin. The results of quantitative real-time PCR showed increased expression of E-cadherin following treatment with oxamflatin at the concentration of 2.5 mM compared with 1 mM. The present results showed that oxamflatin can induce E-cadherin expression and also reduce cell viability in the MKN-45 cell line. On the basis of these findings, oxamflatin can be further considered for the prevention of tumor metastasis.
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References
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM . Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127: 2893–2917.
Moghimi-Dehkordi B, Safaee A, Zali MR . Survival rates and prognosis of gastric cancer using an actuarial life-table method. Asian Pac J Cancer Prev. 2008; 9: 317–321.
Yazdizadeh B, Jarrahi AM, Mortazavi H, Mohagheghi MA, Tahmasebi S, Nahvijo A . Time trends in the occurrence of major GI cancers in Iran. Asian Pac J Cancer Prev. 2005; 6: 130–134.
Kaufmann M, Von Minckwitz G, Smith R, Valero V, Gianni L, Eiermann W et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 2003; 21: 2600–2608.
Salarini R, Sahebkar A, Mirzaei H, Jaafari M, Riahi M, Hadjati J et al. Epi-drugs and Epi-miRs: moving beyond current cancer therapies. Curr Cancer Drug Target 2015 (e-pub ahead of print).
Mirzaei H, Yazdi F, Salehi R, Mirzaei HR . SiRNA and epigenetic aberrations in ovarian cancer. J Cancer Res Ther 2016; 12: 498–508.
Bolden JE, Peart MJ, Johnstone RW . Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 2006; 5: 769–784.
Riggs MG, Whittaker RG, Neumann JR, Ingram VM . n-Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells. Nature 1977; 268: 462–464.
Kim YB, Lee K-H, Sugita K, Yoshida M, Horinouchi S . Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase. Oncogene 1999; 18: 2461–2470.
Sonoda H, Nishida K, Yoshioka T, Ohtani M, Sugita K . Oxamflatin: a novel compound which reverses malignant phenotype to normal one via induction of JunD. Oncogene 1996; 13: 143–149.
Wang Y-L, Liui H-L, Fu R-G, Wang Z-W, Ren H-T, Dai Z-J et al. HDAC inhibitor oxamflatin induces morphological changes and has strong cytostatic effects in ovarian cancer cell lines. Curr Mol Med 2016; 16: 232–242.
Peart MJ, Tainton KM, Ruefli AA, Dear AE, Sedelies KA, O’Reilly LA et al. Novel mechanisms of apoptosis induced by histone deacetylase inhibitors. Cancer Res 2003; 63: 4460–4471.
Zhu J-S, Wang L, Cheng G-Q, Li Q, Zhu Z-M, Zhu L . Apoptosis mechanisms of human gastric cancer cell line MKN-45 infected with human mutant p27. World J Gastroenterol 2005; 11: 7536.
Gregory PD, Wagner K, Horz W . Histone acetylation and chromatin remodeling. Exp Cell Res 2001; 265: 195–202.
Takai N, Ueda T, Kawano Y, Nishida M, Nasu K, Narahara H . C2-ceramide exhibits antiproliferative activity and potently induces apoptosis in endometrial carcinoma. Oncol Rep 2005; 14: 1287–1291.
Tate CR, Rhodes LV, Segar HC, Driver JL, Pounder FN, Burow ME et al. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res 2012; 14: R79.
Komatsu N, Kawamata N, Takeuchi S, Yin D, Chien W, Miller CW et al. SAHA, a HDAC inhibitor, has profound anti-growth activity against non-small cell lung cancer cells. Oncol Rep 2006; 15: 187–191.
Tsai LK, Leng Y, Wang Z, Leeds P, Chuang DM . The mood stabilizers valproic acid and lithium enhance mesenchymal stem cell migration via distinct mechanisms. Neuropsychopharmacology 2010; 35: 2225–2237.
Moody TW, Switzer C, Santana-Flores W, Ridnour LA, Berna M, Thill M et al. Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells. Lung Cancer 2010; 68: 154–160.
Zhang L, Wang G, Wang L, Song C, Wang X, Kang J . Valproic acid inhibits prostate cancer cell migration by up-regulating E-cadherin expression. Pharmazie 2011; 66: 614–618.
Feng S, Yang Y, Lv J, Sun L, Liu M . Valproic acid exhibits different cell growth arrest effect in three HPV-positive/negative cervical cancer cells and possibly via inducing Notch1 cleavage and E6 downregulation. Cancer 2016; 6: 7.
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Faghihloo, E., Araei, Y., Mohammadi, M. et al. The effect of oxamflatin on the E-cadherin expression in gastric cancer cell line. Cancer Gene Ther 23, 396–399 (2016). https://doi.org/10.1038/cgt.2016.52
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DOI: https://doi.org/10.1038/cgt.2016.52
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