- Volume 13 Issue 12
DOI QR Code
Microarray and Quantitative PCR Analysis of Gene Expression Profiles in Response to Treatment with Tomato Leaf Extract in MCF-7 Breast Cancer Cells
- Amid, Azura (Bioprocess and Molecular Engineering Research Unit (BPMERU)) ;
- Chik, Wan Dalila Wan (Bioprocess and Molecular Engineering Research Unit (BPMERU)) ;
- Jamal, Parveen (International Institute for Halal Research and Training, International Islamic University Malaysia) ;
- Hashim, Yumi Zuhanis Has-Yun (Bioprocess and Molecular Engineering Research Unit (BPMERU))
- Published : 2012.12.31
We previously found cytotoxic effects of tomato leaf extract (TLE) on the MCF-7 breast cancer cell line. The aim of this study was to ascertain the molecular mechanisms associated with the usage of TLE as an anticancer agent by microarray analysis using mRNA from MCF-7 breast cancer cells after treatment with TLE for 1 hr and 48 hrs. Approximately 991 genes out of the 30,000 genes in the human genome were significantly (p<0.05) changed after the treatment. Within this gene set, 88 were significantly changed between the TLE treated cells and the untreated MCF-7 cells (control cells) with a cut-off fold change >2.00. In order to focus on genes that were involved in cancer cell growth, only twenty-nine genes were selected, either down-regulated or up-regulated after treatment with TLE. Microarray assay results were confirmed by analyzing 10 of the most up and down regulated genes related to cancer cells progression using real-time PCR. Treatment with TLE induced significant up-regulation in the expression of the CRYAB, PIM1, BTG1, CYR61, HIF1-
Cancer;cytotoxic;MCF-7;microarray;real-time PCR;transcriptomics;tomato leaves
- Zar JH (1999). Biostatistical Analysis New Jersey: Prentice Hall.
- Zhang CX, Ho SC, Chen YM, et al (2009). Greater vegetable and fruit intake is associated with a lower risk of breast cancer among Chinese women. Int J Cancer, 125, 181-8. https://doi.org/10.1002/ijc.24358
- Zhang P, Wang C, Gao K, et al (2010). The ubiquitin ligase itch regulates apoptosis by targeting thioredoxin-interacting protein for ubiquitin-dependent degradation. J Biological Chemistry, 285, 8869-79. https://doi.org/10.1074/jbc.M109.063321
- Zhu S, Yoon K, Sterneck E, Johnson PE, Smart RC (2002). CCAAT/enhancer binding protein-beta is a mediator of keratinocyte survival and skin tumorigenesis involving oncogenic Ras signaling. Proceeding of the National Academy Sci USA, 99, 207-12. https://doi.org/10.1073/pnas.012437299
- Sharoni Y, Linnewiel-Hermoni K, Zango G, et al (2012). The role of lycopene and its derivatives in the regulation of transcription systems: implications for cancer prevention. Am J Clin Nutr, 96, 1173-8. https://doi.org/10.3945/ajcn.112.034645
- Shieh JM, Cheng TH, Shi MD, et al (2011). Alpha-tomatine suppresses invasion and migration of human non-small cell lung cancer NCI-H460 cells through inactivating FAK/PI3K/ Akt signaling pathway and reducing binding activity of NFkappa B. Cell Biochem Biophys, 60, 297-310. https://doi.org/10.1007/s12013-011-9152-1
- Shirogane T, Fukada T, Muller JM, et al (1999). Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis. Immunity, 11, 709-19. https://doi.org/10.1016/S1074-7613(00)80145-4
- Shuman JD, Sebastian T, Kaldis P, et al (2004). Cell cycledependent phosphorylation of C/EBPbeta mediates oncogenic cooperativity between C/EBPbeta and H-RasV12. Molecular Cell Biology, 24, 7380-91. https://doi.org/10.1128/MCB.24.17.7380-7391.2004
- Szpirer C, Riviere M, Cortese R, et al (1992). Chromosomal localization in man and rat of the genes encoding the liverenriched transcription factors C/EBP, DBP, and HNF1/ LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF). Genomics, 13, 293-300. https://doi.org/10.1016/0888-7543(92)90245-N
- Teodoro AJ, Oliveira FL, Martins NB, et al (2012). Effect of lycopene on cell viability and cell cycle progression in human cancer cell lines. Cancer Cell Int, 12, 36. https://doi.org/10.1186/1475-2867-12-36
- Thornton S, Sowders D, Aronow B, et al (2002). DNA microarray analysis reveals novel gene expression profiles in collageninduced arthritis. Clinical Immunology, 105, 155-68. https://doi.org/10.1006/clim.2002.5227
- Tong X, Xie D, O'Kelly J, et al (2001). Cyr61, a member of CCN family, is a tumor suppressor in non-small cell lung cancer. J Biological Chemistry, 276, 47709-14. https://doi.org/10.1074/jbc.M107878200
- Tuzcu M, Aslan A, Tuzcu Z, et al (2012). Tomato powder impedes the development of azoxymethane-induced colorectal cancer in rats through suppression of COX-2 expression via NF-kappaB and regulating Nrf2/HO-1 pathway. Mol Nutr Food Res, 56, 1477-81. https://doi.org/10.1002/mnfr.201200130
- Urig S, Becker K (2006). On the potential of thioredoxin reductase inhibitors for cancer therapy. Seminar in Cancer Biology, 16, 452-65. https://doi.org/10.1016/j.semcancer.2006.09.004
- Verdone L, Agricola E, Caserta M, E Di Mauro (2006). Histone acetylation in gene regulation. Briefings in Functional Genomic Proteomic, 5, 209-21. https://doi.org/10.1093/bfgp/ell028
- Wang H, Bloom O, Zhang M, et al (1999). HMG-1 as a late mediator of endotoxin lethality in mice. Sci, 285, 248-51. https://doi.org/10.1126/science.285.5425.248
- Watanabe G, Kato S, Nakata H, et al (2009). Alpha B-crystallin: a novel p53-target gene required for p53-dependent apoptosis. Cancer Sci, 100, 2368-75. https://doi.org/10.1111/j.1349-7006.2009.01316.x
- Wouters BG, Koritzinsky M (2008). Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nature Reviews Cancer, 8, 851-64. https://doi.org/10.1038/nrc2501
- Xu QY, Gao Y, Liu Y, Yang WZ, Xu WY (2008). Identification of differential gene expression profiles of radioresistant lung cancer cell line established by fractionated ionizing radiation in vitro. Chinese Med J (Engl), 121, 1830-7.
- Lamb J, Ramaswamy S, Ford HL, et al (2003). A mechanism of cyclin D1 action encoded in the patterns of gene expression in human cancer. Cell, 114, 323-34. https://doi.org/10.1016/S0092-8674(03)00570-1
- Lee W, Ku SK, Bae JW, Bae JS (2012). Inhibitory effects of lycopene on HMGB1-mediated pro- inflammatory responses in both cellular and animal models. Food Chem Toxicol, 50, 1826-33. https://doi.org/10.1016/j.fct.2012.03.003
- Lim KP, Cirillo N, Hassona Y, et al (2011). Fibroblast gene expression profile reflects the stage of tumour progression in oral squamous cell carcinoma. J Pathology, 223, 459-69. https://doi.org/10.1002/path.2841
- Liu L, Cash TP, Jones RG, et al (2006). Hypoxia-induced energy stress regulates mRNA translation and cell growth. Molecular Cell, 21, 521-31. https://doi.org/10.1016/j.molcel.2006.01.010
- Lock C, Hermans G, Pedotti R, et al (2002). Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nature Med, 8, 500-8. https://doi.org/10.1038/nm0502-500
- Lotze MT, Tracey KJ (2005). High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nature Reviews Immunology, 5, 331-42.
- Luft F (2010). The rise of a ribosomopathy and increased cancer risk. J Molecular Med, 88, 1-3. https://doi.org/10.1007/s00109-009-0570-0
- Lv H, Sun S, Ma X, et al (2009). Cyr61 is up-regulated in prostate cancer and associated with the p53 gene status, 106, 738-44. https://doi.org/10.1002/jcb.22075
- Menendez JA, Mehmi I, Griggs DW, Lupu R (2003). The angiogenic factor CYR61 in breast cancer: molecular pathology and therapeutic perspectives. Endocrine-Related Cancer, 10, 141-52. https://doi.org/10.1677/erc.0.0100141
- Osley MA (1991). The regulation of histone synthesis in the cell cycle. Annual Review of Biochemistry, 60, 827-61. https://doi.org/10.1146/annurev.bi.60.070191.004143
- Palozza P, Parrone N, Simone R, Catalano A (2011). Role of lycopene in the control of ROS-mediated cell growth: implications in cancer prevention. Curr Med Chem, 18, 1846-60. https://doi.org/10.2174/092986711795496845
- Palozza P, Simone R, Catalano A, Russo M, Bohm V (2012). Lycopene modulation of molecular targets affected by smoking exposure. Curr Cancer Drug Targets, 12, 640-57. https://doi.org/10.2174/156800912801784866
- Powis G, Kirkpatrick DL (2007). Thioredoxin signaling as a target for cancer therapy. Current Opinion Pharmacology, 7, 392-7. https://doi.org/10.1016/j.coph.2007.04.003
- Rajeswari MR, Jain A (2001). High-mobility-group chromosomal proteins, HMGA1 as potential tumour markers. Current Sci, 82, 838-44.
- Rao AV, Balachandran B (2002). Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutritional Neuroscience, 5, 291-309. https://doi.org/10.1080/1028415021000033767
- Robert DD (1996). Regulation of tumor growth and metastasis by thrombospondin-1. J Federation of Am Soc for Experimental Biology, 10, 1183-91.
- Rouault JP, R Rimokh, C Tessa, et al (1992). BTG1, a member of a new family of antiproliferative genes. EMBO J, 11, 1663-70.
- Schenone S, Tintori C, Botta M (2010). Using insights into Pim1 structure to design new anticancer drugs. Current Pharmaceutical Design, 16, 3964-78. https://doi.org/10.2174/138161210794454996
- Arsham AM, Howell JJ, Simon MC (2003). A novel hypoxiainducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets. J Biological Chemistry, 278, 29655-60. https://doi.org/10.1074/jbc.M212770200
- Cadenas C, Franckenstein D, Schmidt M, et al (2010). Role of thioredoxin reductase 1 and thioredoxin interacting protein in prognosis of breast cancer. Breast Cancer Res, 12, 44.
- Cao Z, Umek RM, McKnight SL (1991). Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes and Development, 5, 1538-52. https://doi.org/10.1101/gad.5.9.1538
- Chao MW, Chen CH, Chang YL, Teng CM, Pan SL (2012). Alpha-tomatine-mediated anti- cancer activity in vitro and in vivo through cell cycle- and caspase-independent pathways. PLoS One, 7, 44093. https://doi.org/10.1371/journal.pone.0044093
- Chik WD, Amid WA, Jamal P (2010). Purification and cytotoxicity assay of tomato (Lycopersicon esculen tum) leaves methanol extract as potential anticancer agent. J Applied Sci, 10, 3283-8. https://doi.org/10.3923/jas.2010.3283.3288
- Clarke PA, R te Poele, Workman P (2004). Gene expression microarray technologies in the development of new therapeutic agents. Eur J Cancer, 40, 2560-91. https://doi.org/10.1016/j.ejca.2004.07.024
- Dameron KM, Volpert OV, Tainsky MA, Bouck N (1994). Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Sci, 265, 1582-4. https://doi.org/10.1126/science.7521539
- de Groot RP, Coffer PJ, Koenderman L (1998). Regulation of proliferation, differentiation and survival by the IL-3/IL-5/ GM-CSF receptor family. Cell Signal, 10, 619-28. https://doi.org/10.1016/S0898-6568(98)00023-0
- Freedman ND, Park Y, Subar AF, et al (2008). Fruit and vegetable intake and head and neck cancer risk in a large United States prospective cohort study. Int J Cancer, 122, 2330-6.
- Friedman M (1995). The 142nd General hospital. Maryland Med J, 44, 899-903.
- Friedman M, Carol EL, Lee S-U, et al (2009). Tomatinecontaining green tomato extracts inhibit growth of human breast, colon, liver, and stomach cancer cells. J Agricultural Food Chemistry, 57, 5727-33. https://doi.org/10.1021/jf900364j
- Iadevaia VS, Caldarola L, Biondini A, et al (2010). PIM1 kinase is destabilized by ribosomal stress causing inhibition of cell cycle progression. Oncogene, 29, 5490-9. https://doi.org/10.1038/onc.2010.279
- Jia L, Waxman DJ (2012). Thrombospondin-1 and pigment epithelium-derived factor enhance responsiveness of KM12 colon tumor to metronomic cyclophosphamide but have disparate effects on tumor metastasis. Cancer Lett.
- Juliano RL (2002). Signal transduction by cell adhesion receptors and the cytoskeleton: functions of integrins, cadherins, selectins, and immunoglobulin-superfamily members. Annu Rev Pharmacol Toxicol, 42, 283-323. https://doi.org/10.1146/annurev.pharmtox.42.090401.151133
- Kelkel M, Schumacher M, Dicato M, Diederich M (2011). Antioxidant and anti-proliferative properties of lycopene. Free Radic Res, 45, 925-40. https://doi.org/10.3109/10715762.2011.564168
- Analysis of Key Genes and Pathways Associated with Colorectal Cancer with Microarray Technology vol.14, pp.3, 2013, https://doi.org/10.7314/APJCP.2013.14.3.1819
- An Integrating Approach for Genome-Wide Screening of MicroRNA Polymorphisms Mediated Drug Response Alterations vol.2017, pp.2314-4378, 2017, https://doi.org/10.1155/2017/1674827