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Drug Res (Stuttg) 2017; 67(09): 509-514
DOI: 10.1055/s-0042-119647
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Chrysin Alters microRNAs Expression Levels in Gastric Cancer Cells: Possible Molecular Mechanism

Farideh Mohammadian
1   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Younes Pilehvar-Soltanahmadi
1   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Shahriar Alipour
3   Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Mehdi Dadashpour
1   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
,
Nosratollah Zarghami
1   Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 12 August 2016

accepted 19 October 2016

Publication Date:
19 June 2017 (online)

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Abstract

Background Gastric carcinoma still remains the second most common cause of cancer mortality in the world. Chrysin, as a flavone, has showed cancer chemopreventive activity. The cellular and molecular mechanisms of chrysin in cancer cells have not been fully understood.

Objective In this study, we investigate expression levels of let-7a, miR-9, mir-18a, miR-21, miR-22, miR-34a, miR-126 and mir-221 to describe the anti-cancer effects of chrysin.

Materials and Methods The cytotoxic effects of chrysin were assessed using MTT assay. The effect of chrysin on the microRNAs expression was determined by qRT-PCR.

Results The MTT results for different concentrations of chrysin at different times on the Gastric carcinoma cells showed that IC50 for chrysin was 68.24 µM after 24 h of treatment. Expression analysis identified that miR-18, miR-21 and miR-221 were down regulated whereas let-7a, miR-9, miR-22, miR-34a and miR-126 were up regulated in Gastric carcinoma cell line (p<0.05).

Conclusion Treatment with chrysin can alter the miRNAs expression and these findings might be an explanation for molecular mechanism of chrysin effect on gastric cancer.

Key words

gastric cancer - chrysin - microRNA
 

  • References

  • 1 Mohammadian F, Abhari A, Dariushnejad H. et al. Effects of Chrysin-PLGA-PEG Nanoparticles on Proliferation and Gene Expression of miRNAs in Gastric Cancer Cell Line. Iranian journal of cancer prevention 2016; 9: e4190
    PubMedGoogle Scholar
  • 2 Ema A, Yamashita K, Sakuramoto S. et al. Lymph node ratio is a critical prognostic predictor in gastric cancer treated with S-1 chemotherapy. Gastric Cancer 2014; 17: 67-75
    CrossrefPubMedGoogle Scholar
  • 3 Mohammadian F, Abhari A, Dariushnejad H. et al. Upregulation of Mir-34a in AGS Gastric Cancer Cells by a PLGA-PEG-PLGA Chrysin Nano Formulation. Asian Pacific journal of cancer prevention: APJCP 2014; 16: 8259-8263
    PubMedGoogle Scholar
  • 4 Li Y, Kong D, Wang Z. et al. Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research. Pharm Res 2010; 27: 1027-1041
    CrossrefPubMedGoogle Scholar
  • 5 Arezoomand R, Zarghami N, Rahmati M. et al. The inhibitory effect of Curcuma longa total extract on telomerase gene expression and activity in MCF-7 breast cancer cell line. Pharmaceutical Sciences 2010; 16: 131-138
    PubMedGoogle Scholar
  • 6 Mollazade M, Nejati-Koshki K, Akbarzadeh A. et al. PAMAM dendrimers arugment inhibitory effect of curcumin on cancer cell proliferation: possible inhibition of telomerase. Asian Pac J Cancer Prev 2013; 14: 6925-6928
    CrossrefPubMedGoogle Scholar
  • 7 Ambros V. The functions of animal microRNAs. Nature 2004; 431: 350-355
    CrossrefPubMedGoogle Scholar
  • 8 Sheervalilou R, Ansarin K, Fekri AS. et al. An update on sputum MicroRNAs in lung cancer diagnosis. Diagnostic cytopathology 2016; 44: 442-449
    CrossrefPubMedGoogle Scholar
  • 9 Di Leva G, Croce CM. miRNA profiling of cancer. Curr Opin Genet Dev 2013; 23: 3-11
    CrossrefPubMedGoogle Scholar
  • 10 Yang Q, Jie Z, Cao H. et al. Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C. Carcinogenesis 2011; 32: 713-722
    CrossrefPubMedGoogle Scholar
  • 11 Zhang Z, Li Z, Gao C. et al. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest 2008; 88: 1358-1366
    CrossrefPubMedGoogle Scholar
  • 12 Petrocca F, Visone R, Onelli MR. et al. E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 2008; 13: 272-286
    CrossrefPubMedGoogle Scholar
  • 13 Du Y, Xu Y, Ding L. et al. Down-regulation of miR-141 in gastric cancer and its involvement in cell growth. J Gastroenterol 2009; 44: 556-561
    CrossrefPubMedGoogle Scholar
  • 14 Bandres E, Bitarte N, Arias F. et al. microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res 2009; 15: 2281-2290
    CrossrefPubMedGoogle Scholar
  • 15 Takagi T, Iio A, Nakagawa Y. et al. Decreased expression of microRNA-143 and -145 in human gastric cancers. Oncology 2009; 77: 12-21
    CrossrefPubMedGoogle Scholar
  • 16 Luo H, Zhang H, Zhang Z. et al. Down-regulated miR-9 and miR-433 in human gastric carcinoma. J Exp Clin Cancer Res 2009; 28: 82
    CrossrefPubMedGoogle Scholar
  • 17 Alibakhshi A, Ranjbari J, Pilehvar-Soltanahmadi Y. et al. An Update on Phytochemicals Substances in Molecular Target Therapy of Cancer: Potential Inhibitory Effect on Telomerase Activity. Current medicinal chemistry 2016; 23: 2380-2393
    CrossrefPubMedGoogle Scholar
  • 18 Samarghandian S, Afshari JT, Davoodi S. Chrysin reduces proliferation and induces apoptosis in the human prostate cancer cell line pc-3. Clinics (Sao Paulo) 2011; 66: 1073-1079
    CrossrefPubMedGoogle Scholar
  • 19 Cho H, Yun CW, Park WK. et al. Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives. Pharmacol Res 2004; 49: 37-43
    CrossrefPubMedGoogle Scholar
  • 20 Mohammadian F, Pilehvar-Soltanahmadi Y, Zarghami F. et al. Upregulation of miR-9 and Let-7a by nanoencapsulated chrysin in gastric cancer cells. Artificial Cells, Nanomedicine, and Biotechnology 2016; 44: 1-6
    CrossrefPubMedGoogle Scholar
  • 21 Khoo BY, Chua SL, Balaram P. Apoptotic effects of chrysin in human cancer cell lines. Int J Mol Sci 2010; 11: 2188-2199
    CrossrefPubMedGoogle Scholar
  • 22 Motoyama K, Inoue H, Nakamura Y. et al. Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family. Clin Cancer Res 2008; 14: 2334-2340
    CrossrefPubMedGoogle Scholar
  • 23 Yao Y, Suo AL, Li ZF. et al. MicroRNA profiling of human gastric cancer. Molecular medicine reports 2009; 2: 963-970
    PubMedGoogle Scholar
  • 24 Khoo BY, Chua SL, Balaram P. Apoptotic effects of chrysin in human cancer cell lines. International journal of molecular sciences 2010; 11: 2188-2199
    CrossrefPubMedGoogle Scholar
  • 25 Yao Y, Suo AL, Li ZF. et al. MicroRNA profiling of human gastric cancer. Mol Med Rep 2009; 2: 963-970
    PubMedGoogle Scholar
  • 26 Beishline K, Azizkhan-Clifford J. Sp1 and the ‘hallmarks of cancer’. Febs j 2015; 282: 224-258
    CrossrefPubMedGoogle Scholar
  • 27 Wu X-m, Shao X-q, Meng X-x. et al. Genome-wide analysis of microRNA and mRNA expression signatures in hydroxycamptothecin-resistant gastric cancer cells. Acta Pharmacologica Sinica 2011; 32: 259-269
    CrossrefPubMedGoogle Scholar
  • 28 Wu F, Huang W, Wang X. microRNA-18a regulates gastric carcinoma cell apoptosis and invasion by suppressing hypoxia-inducible factor-1α expression. Experimental and therapeutic medicine 2015; 10: 717-722
    CrossrefPubMedGoogle Scholar
  • 29 Zheng Y, Li S, Ding Y. et al. The role of miR-18a in gastric cancer angiogenesis. Hepato-gastroenterology 2013; 60: 1809-1813
    PubMedGoogle Scholar
  • 30 Zhong Z, Dong Z, Yang L. et al. miR-21 induces cell cycle at S phase and modulates cell proliferation by down-regulating hMSH2 in lung cancer. Journal of cancer research and clinical oncology 2012; 138: 1781-1788
    CrossrefPubMedGoogle Scholar
  • 31 Shen H, Zhu F, Liu J. et al. Alteration in Mir-21/PTEN expression modulates gefitinib resistance in non-small cell lung cancer. PLoS One 2014; 9: e103305
    CrossrefPubMedGoogle Scholar
  • 32 Luo H, Zhang H, Zhang Z. et al. Down-regulated miR-9 and miR-433 in human gastric carcinoma. Journal of Experimental & Clinical Cancer Research 2009; 28: 1
    CrossrefPubMedGoogle Scholar
  • 33 Peng Y, Guo J-J, Liu Y-M. et al. MicroRNA-34A inhibits the growth, invasion and metastasis of gastric cancer by targeting PDGFR and MET expression. Bioscience reports 2014; 34: e00112
    CrossrefPubMedGoogle Scholar
  • 34 Cao W, Fan R, Wang L. et al. Expression and regulatory function of miRNA-34a in targeting survivin in gastric cancer cells. Tumor Biology 2013; 34: 963-971
    CrossrefPubMedGoogle Scholar
  • 35 Zuo Q, Cao L, Yu T. et al. MicroRNA-22 inhibits tumor growth and metastasis in gastric cancer by directly targeting MMP14 and Snail. Cell death & disease 2015; 6: e2000
    CrossrefPubMedGoogle Scholar
  • 36 Guo M-M, Hu L-H, Wang Y-Q. et al. miR-22 is down-regulated in gastric cancer, and its overexpression inhibits cell migration and invasion via targeting transcription factor Sp1. Medical oncology 2013; 30: 1-7
    PubMedGoogle Scholar
  • 37 Xiong J. Multiple targeting routes of MicroRNA-22 inform cancer drug discovery. Gene Technology S 2015; 1: 2
    PubMedGoogle Scholar
  • 38 Chun-zhi Z, Lei H, An-ling Z. et al. MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN. BMC cancer 2010; 10: 1
    CrossrefPubMedGoogle Scholar
  • 39 Mohammadian F, Pilehvar-Soltanahmadi Y, Mofarrah M. et al. Down regulation of miR-18a, miR-21 and miR-221 genes in gastric cancer cell line by chrysin-loaded PLGA-PEG nanoparticles. Artificial cells, nanomedicine, and biotechnology 2016; 44: 1972-1978
    CrossrefPubMedGoogle Scholar
  • 40 Liu LY, Wang W, Zhao LY. et al. Mir-126 inhibits growth of SGC-7901 cells by synergistically targeting the oncogenes PI3KR2 and Crk, and the tumor suppressor PLK2. International journal of oncology 2014; 45: 1257-1265
    CrossrefPubMedGoogle Scholar
  • 41 Lei Y, Chen H, Shi F. et al. Reduced miR-126 expression facilitates angiogenesis of gastric cancer through its regulation on VEGF-A. RNA & disease 2015; 2: 11873-11885
    PubMedGoogle Scholar