- Volume 16 Issue 15
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Time - and Concentration - Dependent Effects of Resveratrol on miR 15a and miR16-1 Expression and Apoptosis in the CCRF-CEM Acute Lymphoblastic Leukemia Cell Line
- Azimi, Ako ;
- Hagh, Majid Farshdousti ;
- Talebi, Mehdi ;
- Yousefi, Bahman ;
- feizi, Abbas Ali Hossein pour ;
- Baradaran, Behzad ;
- Movassaghpour, Ali Akbar ;
- Shamsasenjan, Karim ;
- Khanzedeh, Taghi ;
- Ghaderi, Abdol Hasan ;
- Heydarabad, Milad Zadi
- Published : 2015.10.06
Background: Chemotherapy is one of the common approaches in treatment of cancers, especially leukemia. However, drug resistance phenomena reduce the likelihood of treatment success. Resveratrol is a herbal compound which through complicated processes makes some selected cells sensitive to treatment and induction of apoptosis. In the present study, the effects of resveratrol on the expression of miR 15a and miR16-1 and apoptosis in the CCRF-CEM cell line were investigated. Materials and Methods: The CCRF-CEM cell line was cultured under standard conditions and changes in miR 15a and miR 16-1 expression were analyzed by real time-PCR technique, with attention to reveratrol dose and time dependence. Also, apoptosis is evaluated by flow cytometry using annexin V and PI. Results: CCRF-CEM cells underwent dose-dependent apoptotic cell death in response to resveratrol. MiR 15a and miR 16-1 expression was up-regulated after 24 and 48 hours resveratrol treatment (p<0.05). Conclusions: The results of our study indicate that resveratrol induces apoptosis in a time and dose-dependent manner in CCRF-CEM cells. Also, increased expression level of miR 16-1 and miR 15a by means of resveratrol in CCRF-CEM cells might have a role in apoptosis induction and predisposition. According to our results resveratrol can be regarded as a dietary supplement to improve efficacy of anti-leukemia therapies.
ALL;resveratrol;miR 15a;miR 16-1;apoptosis
- Ambros V (2004). The functions of animal microRNAs. Nature, 431, 350-5. https://doi.org/10.1038/nature02871
- Burdelya L, Kujawski M, Niu G, et al (2005). Stat3 activity in melanoma cells affects migration of immune effector cells and nitric oxide-mediated antitumor effects. J Immunol, 174, 3925-31. https://doi.org/10.4049/jimmunol.174.7.3925
- Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281-97. https://doi.org/10.1016/S0092-8674(04)00045-5
- Bernhard D, Tinhofer I, Tonko M, et al (2000). Resveratrol causes arrest in the S-phase prior to Fas-independent apoptosis in CEM-C7H2 acute leukemia Cells. Cell Death Differ, 7, 834-842. https://doi.org/10.1038/sj.cdd.4400719
- Chin YT, Hsieh MT, Yang SH, et al(2014). Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro. Oncotarget, 5, 12891-907.
- Cullberg KB, Foldager CB, Lind M, Richelsena B, Pedersena SB (2014). Inhibitory effects of resveratrol on hypoxia-induced inflammation in 3T3-L1 adipocytes and macrophages. J Funct Foods, 7, 171-79. https://doi.org/10.1016/j.jff.2014.02.015
- Calin GA, Cimmino A, Fabbri M, et al. (2008). MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci U S A, 105, 5166-71. https://doi.org/10.1073/pnas.0800121105
- Chivukula RR, Mendell JT (2008). Circular reasoning: microRNAs and cellcycle control. Trends Biochem Sci, 33, 474-81. https://doi.org/10.1016/j.tibs.2008.06.008
- Cecchinato V, Chiaramonte R, Nizzardo M, et al (2007). Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells. Biochemical Pharmacol, 74, 1568-74. https://doi.org/10.1016/j.bcp.2007.08.001
- Cui J, Fu H, Feng J, et al (2007). The construction of miRNA expression library for human. Progr. Biochem. Biophys, 34, 389-94.
- Cimmino A, Calin GA, Fabbri M, et al (2005). MiR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A, 102, 13944-49. https://doi.org/10.1073/pnas.0506654102
- Calin GA, Dumitru CD, Shimizu M, et al (2002). Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A, 99, 15524-29. https://doi.org/10.1073/pnas.242606799
- Clement MV, Hirpara JL, Chawdhury SH, Pervaiz S (1998). Chemopreventive agent resveratrol, a natural product derived from grapes, triggers CD95 signaling-dependent apoptosis in human tumor cells. Blood, 92, 996-1002.
- Della RF, Cucciolla V, Borriello A, et al (1998). Resveratrol arrests the cell division cycle at S/G2 phase transition. Biochem Biophys Res Commun, 250, 53-8. https://doi.org/10.1006/bbrc.1998.9263
- Dirks W, Schone S, Uphoff C, et al (1997). Expression and function of CD95 (FAS/APO-1) in leukaemia-lymphoma tumour lines. Br J Haematol, 96, 584-593. https://doi.org/10.1046/j.1365-2141.1997.d01-2048.x
- Estrov Z, Shishodia S, Faderl S, et al (2003). Resveratrol blocks interleukin-1h-induced activation of the nuclear transcription factor NF-nB, inhibits proliferation, causes S-phase arrest, and induces apoptosis of acute myeloid leukemia cells. Blood, 102, 987-95. https://doi.org/10.1182/blood-2002-11-3550
- Fouad MA, Agha AM, Merzabani MM, Shouman SA (2013). Resveratrol inhibits proliferation, angiogenesis and induces apoptosis in colon cancer cells: calorie restriction is the force to the cytotoxicity. Hum Exp Toxicol, 32, 1067-80. https://doi.org/10.1177/0960327113475679
- Fulda S (2010). Resveratrol and derivatives for the prevention and treatment of cancer. Drug Discov Today, 15, 757-65. https://doi.org/10.1016/j.drudis.2010.07.005
- Fremont L (2000). Biological effects of resveratrol. Life Sciences, 66, 663-73. https://doi.org/10.1016/S0024-3205(99)00410-5
- Fontecave M, Lepoivre M, Elleingand E, Gerez C, Guittet O (1998). Resveratrol, a remarkable inhibitor of ribonucleotide reductase. FEBS Lett, 421, 277-9. https://doi.org/10.1016/S0014-5793(97)01572-X
- Guang-Hua F, Zhong-Ming W, Xi Y, et al (2014). Resveratrol inhibits oesophageal adenocarcinoma cell proliferation via AMP-activated protein kinase signaling. Asian Pac J Cancer Prev, 15, 677-82. https://doi.org/10.7314/APJCP.2014.15.2.677
- Hai-Tao Y, Qing-Zhong T, Luan G, et al (2013). In vitro and in vivo evaluation of the antitumor efficiency of resveratrol against lung cancer. Asian Pac J Cancer Prev, 14, 1703-06. https://doi.org/10.7314/APJCP.2013.14.3.1703
- He L, Hannon GJ (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet, 5, 522-31. https://doi.org/10.1038/nrg1379
- Hsieh TC, Juan G, Darzynkiewicz Z, Wu JM (1999). Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2. Cancer Res, 59, 2596-601.
- Inui M, Martello G, Piccolo S (2010). MicroRNA control of signal transduction. Nat Rev Mol Cell Biol, 11, 252-63. https://doi.org/10.1038/nrn2804
- Jie-Yu F, Zhi-Hua L, Qiang L, et al (2012). Resveratrol affects protein kinase C activity and promotes apoptosis in human colon carcinoma cells. Asian Pac J Cancer Prev, 13, 6017-22. https://doi.org/10.7314/APJCP.2012.13.12.6017
- Juan ME, Alfaras I, Planas JM (2012). Colorectal cancer chemoprevention by trans-resveratrol. Pharmacol Res, 65, 584-91. https://doi.org/10.1016/j.phrs.2012.03.010
- Keitaro H, Nobuyoshi K (2012). Stilbene derivatives promote Ago 2-dependent tumour-suppressive microRNA activity. Sci Rep, 2, 314.
- Lephart ED, Sommerfeldt JM, Andrus MB (2014). Resveratrol: Influences on gene expression in human skin. J Funct Foods, 10, 377-84. https://doi.org/10.1016/j.jff.2014.07.017
- Liu B, Zhou Z, Zhou W, et al (2014). Resveratrol inhibits proliferation in human colorectal carcinoma cells by inducing G1/S-phase cell cycle arrest and apoptosis through caspase/cyclin- CDK pathways. Mol Med Rep, 10, 1697-702.
- Liu ML, Zhang SJ (2014). Effects of resveratrol on the protein expression of survivin and cell apoptosis in human gastric cancer cells, J Buon, 19, 713-17.
- Lin CY, Hsiao WC, Wright DE, et al (2013). Resveratrol activates the histone H2B ubiquitin ligase, RNF20, in MD A-MB-231 breast cancer cells. J Funct Foods, 5, 790-800. https://doi.org/10.1016/j.jff.2013.01.025
- Lewis BP, Burge CB, Bartel DP (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are micro- RNA targets. Cell, 120, 15-20. https://doi.org/10.1016/j.cell.2004.12.035
- Lin MT, Yen ML, Lin CY, Kuo ML (2003). Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation. Mol Pharmacol, 64, 1029-36. https://doi.org/10.1124/mol.64.5.1029
- Niu G, Wright KL, Ma Y, et al (2005). Role of Stat3 in regulating p53 expression and function. Mol Cell Biol, 25, 7432-40. https://doi.org/10.1128/MCB.25.17.7432-7440.2005
- Ofir M, Hacohen D, Ginsberg D (2011). miR-15 and miR-16 are direct transcriptional targets of E2F1 that Limit E2F-induced proliferation by targeting cyclin E. Mol Cancer Res, 9, 440-7. https://doi.org/10.1158/1541-7786.MCR-10-0344
- Pallares V, Calay D, Cedo L, et al (2012). Enhanced antiinflammatory effect of resveratrol and epa intreated endotoxin-activated raw 256.7 macrophages. Br J Nutr, 14, 1562-73.
- Panaro MA, Carofiglio V, Acquafredda A, Cavallo P, Cianciulli A (2012). Anti-inflammatory effects of resveratrol occur via inhibition of lipopolysaccharide-induced NF-kB activation in Caco-2 and SW480 human colon cancer cells. Br J Nutr, 108, 1623-32. https://doi.org/10.1017/S0007114511007227
- Pui C-H, Robison LL, Look AT (2008). Acute lymphoblastic leukaemia. Lancet, 371, 1030-43. https://doi.org/10.1016/S0140-6736(08)60457-2
- Sevinc S U, Sefa C, Ersin G, et al (2013). Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 Non-small cell lung cancer cells exposed to benzo(a)pyrene. Asian Pac J Cancer Prev, 14, 6159-64. https://doi.org/10.7314/APJCP.2013.14.10.6159
- Subash CG, Ramaswamy K, Simone R, Ji HK, Bharat BA (2011). Chemosensitization of tumors by resveratrol. Ann N Y Acad Sci, 1215, 150-60. https://doi.org/10.1111/j.1749-6632.2010.05852.x
- Stanulla M, Schrappe M (2009). Treatment of childhood acute lymphoblastic leukemia. Semin Hematol, 46, 52-63. https://doi.org/10.1053/j.seminhematol.2008.09.007
- signorelli P, Ghidoni R (2005). Resveratrol as an anticancer nutrient: molecular basis, open question and promises. J Nutr Biochem, 16, 449-66. https://doi.org/10.1016/j.jnutbio.2005.01.017
- Surh YJ, Hurh YJ, Kang JY, et al (1999). Resveratrol. an antioxidant present in red wine, induces apoptosis in human promyelocytic leukemia (HLA60) cells. Cancer Letters, 140, 1-10. https://doi.org/10.1016/S0304-3835(99)00039-7
- Subbaramaiah K, Chung WJ, Michaluart P, et al (1998). Resveratrol inhibits cyclooxygenase2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J Biol Chem, 273, 21875-82. https://doi.org/10.1074/jbc.273.34.21875
- Tsan MF, White JE, Maheshwari JG, Bremner TA, Sacco J (2000). Resveratrol induces fas signaling-independent apoptosis in THP-1 human monocytic leukemia cells. Br J Haematol, 109, 405-12. https://doi.org/10.1046/j.1365-2141.2000.01980.x
- Ulasli SS, Celik S, Gunay E, et al (2013). Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lung cancer cells exposed to benzo(a) pyrene. Asian Pac J Cancer Prev, 14, 6159-64. https://doi.org/10.7314/APJCP.2013.14.10.6159
- Xin-pin Wu, Min Xiong, Cheng-shan Xu, et al (2015). Resveratrol induces apoptosis of human chronic myelogenous leukemia cells in vitro through p38 and JNK-regulated H2AX phosphorylation. Acta Pharmacol Sin, 36, 353-61. https://doi.org/10.1038/aps.2014.132
- Yang Q, Wang B, Zang W, et al (2013). Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1- dependent manner. PLoS One, 8, 70627. https://doi.org/10.1371/journal.pone.0070627
- Yu XM, Jaskula-Sztul R, Ahmed K, et al (2013). Resveratrol induces differentiation markers expression in anaplastic thyroid carcinoma via activation of notch1 signaling and suppresses cell growth. Mol Cancer Ther, 12, 1276-87. https://doi.org/10.1158/1535-7163.MCT-12-0841
- Yu R, Hebbar V, Kim DW, et al (2001). Resveratrol inhibits phorbol ester and UV-induced activator protein 1 activation by interfering with mitogen-activated protein kinase pathways. Mol Pharmacol, 60, 217-24.
- miR-196b/miR-1290 participate in the antitumor effect of resveratrol via regulation of IGFBP3 expression in acute lymphoblastic leukemia vol.37, pp.2, 2016, https://doi.org/10.3892/or.2016.5321
- Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and therapeutic strategy in prostate cancer vol.1403, pp.1, 2017, https://doi.org/10.1111/nyas.13372
- Chemoprevention by resveratrol and pterostilbene: Targeting on epigenetic regulation vol.44, pp.1, 2017, https://doi.org/10.1002/biof.1401
- promoter methylation vol.119, pp.12, 2018, https://doi.org/10.1002/jcb.27333
- The role of tumor suppressor of resveratrol and prednisolone by downregulation of YKL-40 expression in CCRF-CEM cell line pp.07302312, 2018, https://doi.org/10.1002/jcb.27659
- expression and apoptosis in a resveratrol- and prednisolone-treated human T-ALL cell line, CCRF-CEM vol.53, pp.1, 2018, https://doi.org/10.5045/br.2018.53.1.53
- Resveratrol potentially increased the tumoricidal effect of doxorubicin on SKOV3 cancer stem cells in vitro pp.07302312, 2019, https://doi.org/10.1002/jcb.28129
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