Up-regulation of miR-21 decreases chemotherapeutic effect of dendrosomal curcumin in breast cancer cells

Document Type : Original Article

Authors

1 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Medical Biotechnology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran

3 Department of Cellular Biotechnology, Faculty of Chemistry, Kashan University, Kashan, Iran

Abstract

Objective(s): Despite the good results of anticancer activities by curcumin, there are some hurdles that limit the use of curcumin as an anticancer agent. Many methods were examined to overcome this defect like the use of the dendrosomal curcumin (DNC). There is increasing evidence that miRNAs play important roles in biological processes. In this study, we focus on the roles of microRNA-21 in the anti-cancer effects of DNC in breast cancer.
Materials and Methods: Also, we have used different methods such as MTT, apoptosis, cell cycle analysis, transwell migration assay and RT-PCR to find out more.
Results: We observed that miR-21 decreased apoptotic cells in both cells (from 6.35% to 0.34 % and from 7.72% to 1.32% orderly) and DNC increased it. As well as, our findings indicated that cell migration capacity was increased by miR-21 over expression and was decreased by DNC. The combination of miR-21 vector transfection and DNC treatment showed lower percentage of apoptotic cells or a higher level of penetration through the membrane compared with DNC treatment alone. Furthermore, DNC induced a marked increase in the number of cells in sub G1/G1 phase and a decrease in G2/M phase of the cell cycle in both; but, we observed reverse results compared it, after transfection with miR-21 vector.
Conclusion: We observed that miR-21 suppress many aspects of anti-cancer effects of DNC in breast cancer cells, it seems that co-treatment with DNC and mir-21 down-regulation may provide a clinically useful tool for drug-resistance breast cancer cells.

Keywords

References

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet‐Tieulent J, Jemal A. Global cancer statistics, 2012. CA: a cancer journal for clinicians 2015; 65:87-108.
2. Volinia S, Calin GA, Liu C-G, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proceedings of the National academy of Sciences of the United States of America 2006; 103:2257-2261.
3. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. cell 2004; 116:281-297.
4. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nature Reviews Cancer 2006; 6:857-866.
5. Mattie MD, Benz CC, Bowers J, Sensinger K, Wong L, Scott GK, et al. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Molecular cancer 2006; 5:24.
6. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer cell 2006; 9:189-198.
7. Wang Y, Gao X, Wei F, Zhang X, Yu J, Zhao H, et al. Diagnostic and prognostic value of circulating miR-21 for cancer: a systematic review and meta-analysis. Gene 2014; 533:389-397.
8. Zhu X, Lv M, Wang H, Guan W. Identification of circulating microRNAs as novel potential biomarkers for gastric cancer detection: a systematic review and meta-analysis. Digestive diseases and sciences 2014; 59:911-919.
9. Iorio MV, Ferracin M, Liu C-G, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer research 2005; 65:7065-7070.
10. Kutay H, Bai S, Datta J, Motiwala T, Pogribny I, Frankel W, et al. Down-regulation of miR‐122 in the rodent and human hepatocellular carcinomas. Journal of cellular biochemistry 2006; 99:671-678.
11. Zhang Z, Li Z, Gao C, Chen P, Chen J, Liu W, et al. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Laboratory investigation 2008; 88:1358-1366.
12. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. MicroRNA signatures in human ovarian cancer. Cancer research 2007; 67:8699-8707.
13. Nam EJ, Yoon H, Kim SW, Kim H, Kim YT, Kim JH, et al. MicroRNA expression profiles in serous ovarian carcinoma. Clinical cancer research 2008; 14:2690-2695.
14. Lui W-O, Pourmand N, Patterson BK, Fire A. Patterns of known and novel small RNAs in human cervical cancer. Cancer research 2007; 67:6031-6043.
15.Tran N, McLean T, Zhang X, Zhao CJ, Thomson JM, O’Brien C, et al. MicroRNA expression profiles in head and neck cancer cell lines. Biochemical and biophysical research communications 2007; 358:12-17.
16.Tetzlaff MT, Liu A, Xu X, Master SR, Baldwin DA, Tobias JW, et al. Differential expression of miRNAs in papillary thyroid carcinoma compared to multinodular goiter using formalin fixed paraffin embedded tissues. Endocrine pathology 2007; 18:163-173.
17.Kasahara K, Taguchi T, Yamasaki I, Kamada M, Yuri K, Shuin T. Detection of genetic alterations in advanced prostate cancer by comparative genomic hybridization. Cancer genetics and cytogenetics 2002; 137:59-63.
18.Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin S-F, Dunning MJ, et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome biology 2007; 8:1.
19.Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G, et al. Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer research 2007; 67:11612-11620.
20.Cissell KA, Rahimi Y, Shrestha S, Hunt EA, Deo SK. Bioluminescence-based detection of microRNA, miR21 in breast cancer cells. Analytical chemistry 2008; 80:2319-2325.
21.Si M, Zhu S, Wu H, Lu Z, Wu F, Mo Y. miR-21-mediated tumor growth. Oncogene 2007; 26:2799-2803.
22.Noh E-M, Yi MS, Youn HJ, Lee BK, Lee Y-R, Han J-H, et al. Silibinin enhances ultraviolet B-induced apoptosis in mcf-7 human breast cancer cells. Journal of breast cancer 2011; 14:8-13.
23.Buhrmann C, Mobasheri A, Matis U, Shakibaei M. Curcumin mediated suppression of nuclear factor-κB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment. Arthritis research & therapy 2010; 12:1.
24.Kunnumakkara AB, Anand P, Aggarwal BB. Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer letters 2008; 269:199-225.
25.Gupta SC, Patchva S, Koh W, Aggarwal BB. Discovery of curcumin, a component of golden spice, and its miraculous biological activities. Clinical and Experimental Pharmacology and Physiology 2012; 39:283-299.
26.Vogel A, Pelletier J. Examen chimique de la racine de Curcuma. J Pharm 1815; 1:289-300.
27.Masika J, Zhao Y, Hescheler J, Liang H. Modulation of miRNAs by Natural Agents: Nature’s way of dealing with cancer. RNA & DISEASE 2015; 3.
28.Sarbolouki MN, Sadeghizadeh M, Yaghoobi MM, Karami A, Lohrasbi T. Dendrosomes: a novel family of vehicles for transfection and therapy. Journal of Chemical Technology and Biotechnology 2000; 75:919-922.
29.Alizadeh AM, Khaniki M, Azizian S, Mohaghgheghi MA, Sadeghizadeh M, Najafi F. Chemoprevention of azoxymethane-initiated colon cancer in rat by using a novel polymeric nanocarrier–curcumin. European journal of pharmacology 2012; 689:226-232.
30. Babaei E, Sadeghizadeh M, Hassan ZM, Feizi MAH, Najafi F, Hashemi SM. Dendrosomal curcumin significantly suppresses cancer cell proliferation in vitro and in vivo. International immunopharmacology 2012; 12:226-234.
31. Mirgani MT, Isacchi B, Sadeghizadeh M, Marra F, Bilia AR, Mowla SJ, et al. Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells. International journal of nanomedicine 2014; 9:403-417.
32. Farhangi B, Alizadeh AM, Khodayari H, Khodayari S, Dehghan MJ, Khori V, et al. Protective effects of dendrosomal curcumin on an animal metastatic breast tumor. European journal of pharmacology 2015; 758:188-196.
33. Sethi S, Li Y, H Sarkar F. Regulating miRNA by natural agents as a new strategy for cancer treatment. Current drug targets 2013; 14:1167-1174.
34. Mudduluru G, George-William JN, Muppala S, Asangani IA, Kumarswamy R, Nelson LD, et al. Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer. Bioscience reports 2011; 31:185-197.
35. Zhang W, Bai W. MiR-21 suppresses the anticancer activities of curcumin by targeting PTEN gene in human non-small cell lung cancer A549 cells. Clinical and Translational Oncology 2014; 16:708-713.
36. Bao B, Ali S, Kong D, Sarkar SH, Wang Z, Banerjee S, et al. Anti-tumor activity of a novel compound-CDF is mediated by regulating miR-21, miR-200, and PTEN in pancreatic cancer. PloS one 2011; 6:e17850.
37. Gou M, Men K, Shi H, Xiang M, Zhang J, Song J,et al. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo. Nanoscale 2011; 3:1558-1567.
38. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of immunological methods 1983; 65:55-63.
39. Chen H-C. Boyden chamber assay. Cell Migration: Developmental Methods and Protocols 2005:15-22.
40. Lian J, Zhang X, Tian H, Liang N, Wang Y, Liang C, et al. Altered microRNA expression in patients with non-obstructive azoospermia. Reproductive Biology and Endocrinology 2009; 7:1.
41. Song B, Wang C, Liu J, Wang X, Lv L, Wei L, et al. MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression. Journal of Experimental & Clinical Cancer Research 2010; 29:1.
42. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. Real-time quantification of microRNAs by stem–loop RT–PCR. Nucleic acids research 2005; 33:e179-e179.
43. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. RAS is regulated by the let-7 microRNA family. Cell 2005; 120:635-647.
44. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proceedings of the National Academy of Sciences 2002; 99:15524-15529.
45. Zhao S-F, Zhang X, Zhang X-J, Shi X-Q, Yu Z-J, Kan Q-C. Induction of microRNA-9 mediates cytotoxicity of curcumin against SKOV3 ovarian cancer cells. Asian Pacific journal of cancer prevention: APJCP 2013; 15:3363-3368.
46. Kronski E, Fiori ME, Barbieri O, Astigiano S, Mirisola V, Killian PH, et al. miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and-2. Molecular oncology 2014; 8:581-595.
47. Saini S, Arora S, Majid S, Shahryari V, Chen Y, Deng G, et al. Curcumin Modulates MicroRNA-203–Mediated Regulation of the Src-Akt Axis in Bladder Cancer. Cancer prevention research 2011; 4:1698-1709.
48.Liang H-H, Wei P-L, Hung C-S, Wu C-T, Wang W, Huang M-T, et al. MicroRNA-200a/b influenced the therapeutic effects of curcumin in hepatocellular carcinoma (HCC) cells. Tumor Biology 2013; 34:3209-3218.
49. Reuter S, Gupta SC, Park B, Goel A, Aggarwal BB. Epigenetic changes induced by curcumin and other natural compounds. Genes & nutrition 2011; 6:93-108.
50.Roy S, Levi E, Majumdar AP, Sarkar FH. Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF. Journal of hematology & oncology 2012; 5:1.
51. Li X, Xie W, Xie C, Huang C, Zhu J, Liang Z, et al. Curcumin Modulates miR‐19/PTEN/AKT/p53 Axis to Suppress Bisphenol A‐induced MCF‐7 Breast Cancer Cell Proliferation. Phytotherapy Research 2014; 28:1553-1560.
52. Ma J, Fang B, Zeng F, Pang H, Zhang J, Shi Y, et al. Curcumin inhibits cell growth and invasion through up-regulation of miR-7 in pancreatic cancer cells. Toxicology letters 2014; 231:82-91.
53.Kumar S, Keerthana R, Pazhanimuthu A, Perumal P. Overexpression of circulating miRNA-21 and miRNA-146a in plasma samples of breast cancer patients.  2010.
54. Schmittgen TD, Jiang J, Liu Q, Yang L. A high‐throughput method to monitor the expression of microRNA precursors. Nucleic acids research 2004; 32:e43-e43.
55. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer research 2005; 65:6029-6033.
56. Ciafre S, Galardi S, Mangiola A, Ferracin M, Liu C-G, Sabatino G, et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochemical and biophysical research communications 2005; 334:1351-1358.
57. Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, et al. MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. Journal of Clinical Oncology 2006; 24:4677-4684.
Iranian Journal of Basic Medical Sciences
Volume 20, Issue 4
April 2017
Pages 350-359

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