Neurochemical Research

, Volume 38, Issue 2, pp 420–432 | Cite as

Overexpression of miR-7-1 Increases Efficacy of Green Tea Polyphenols for Induction of Apoptosis in Human Malignant Neuroblastoma SH-SY5Y and SK-N-DZ Cells

  • Mrinmay Chakrabarti
  • Walden Ai
  • Naren L. Banik
  • Swapan K. Ray
Original Paper
First Online:
Received:
Revised:
Accepted:

Abstract

Neuroblastoma is an extracranial solid tumor that usually occurs in infants and children. Malignant neuroblastomas remain mostly refractory to currently available chemotherapeutic agents. So, new therapeutic agents and their molecular mechanisms for induction of cell death must be explored for successful treatment of human malignant neuroblastomas. Two polyphenolic compounds, which are abundant in green tea, are (−)-epigallocatechin (EGC) and (−)-epigallocatechin-3-gallate (EGCG) that possess impressive anti-cancer properties. It is not known yet whether EGC and EGCG can modulate the levels of expression of specific microRNAs (miRs) for induction of apoptosis in human malignant neuroblastomas. In this investigation, we revealed that treatment with EGC or EGCG caused induction of apoptosis with significant changes in expression of specific oncogenic miRs (OGmiRs) and tumor suppressor miRs (TSmiRs) in human malignant neuroblastoma SH-SY5Y and SK-N-DZ cell lines. Treatment of both cell lines with either 50 μM EGC or 50 μM EGCG decreased expression of the OGmiRs (miR-92, miR-93, and miR-106b) and increased expression of the TSmiRs (miR-7-1, miR-34a, and miR-99a) leading to induction of extrinsic and intrinsic pathways of apoptosis. Our data also demonstrated that overexpression of miR-93 decreased efficacy while overexpression of miR-7-1 increased efficacy of the green tea polyphenols for induction of apoptosis in both cell lines. In conclusion, our current investigation clearly indicates that overexpression of miR-7-1 can highly potentiate efficacy of EGCG for induction of apoptosis in human malignant neuroblastoma cells.

Keywords

Apoptosis (−)-Epigallocatechin (−)-Epigallocatechin-3-gallate Neuroblastoma Oncogenic and tumor suppressor miRs 
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Notes

Acknowledgments

This work was supported in part by a grant (R01 NS65456) from the National Institutes of Health (Bethesda, MD, USA) and another grant (SCIRF-11-002) from the South Carolina Spinal Cord Injury Research Foundation (Columbia, SC, USA).

Conflict of interest

None.

References

  1. 1.
    Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3:203–216PubMedCrossRefGoogle Scholar
  2. 2.
    Janardhanan R et al (2009) N-Myc down regulation induced differentiation, early cell cycle exit, and apoptosis in human malignant neuroblastoma cells having wild type or mutant p53. Biochem Pharmacol 78:1105–1114PubMedCrossRefGoogle Scholar
  3. 3.
    Kurahashi N et al (2008) Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol 167:71–77PubMedCrossRefGoogle Scholar
  4. 4.
    Golden EB et al (2009) Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood 113:5927–5937PubMedCrossRefGoogle Scholar
  5. 5.
    Slade RF et al (2003) Characterization and inhibition of fatty acid synthase in pediatric tumor cell lines. Anticancer Res 23:1235–1243PubMedGoogle Scholar
  6. 6.
    Kuzuhara T et al (2008) Green tea catechin as a chemical chaperone in cancer prevention. Cancer Lett 261:12–20PubMedCrossRefGoogle Scholar
  7. 7.
    Chen C et al (2003) Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells. Carcinogenesis 24:1369–1378PubMedCrossRefGoogle Scholar
  8. 8.
    Calin GA et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101:2999–3004PubMedCrossRefGoogle Scholar
  9. 9.
    Miska EA et al (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5:R68PubMedCrossRefGoogle Scholar
  10. 10.
    Shohet JM et al (2011) A genome-wide search for promoters that respond to increased MYCN reveals both new oncogenic and tumor suppressor microRNAs associated with aggressive neuroblastoma. Cancer Res 71:3841–3851PubMedCrossRefGoogle Scholar
  11. 11.
    Volinia S et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103:2257–2261PubMedCrossRefGoogle Scholar
  12. 12.
    Schulte JH et al (2008) MYCN regulates oncogenic microRNAs in neuroblastoma. Int J Cancer 122:699–704PubMedCrossRefGoogle Scholar
  13. 13.
    Cheng AM et al (2005) Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33:1290–1297PubMedCrossRefGoogle Scholar
  14. 14.
    Junn E et al (2009) Repression of α-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci USA 106:13052–13057PubMedCrossRefGoogle Scholar
  15. 15.
    Foley NH et al (2010) MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2. Mol Cancer 9:83PubMedCrossRefGoogle Scholar
  16. 16.
    Mestdagh P et al (2010) The miR-17-92 microRNA cluster regulates multiple components of the TGF-β pathway in neuroblastoma. Mol Cell 40:762–773PubMedCrossRefGoogle Scholar
  17. 17.
    Buechner J et al (2011) Tumour-suppressor microRNAs let-7 and miR-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma. Br J Cancer 105:296–303PubMedCrossRefGoogle Scholar
  18. 18.
    Wei JS et al (2008) The MYCN oncogene is a direct target of miR-34a. Oncogene 27:5204–5213PubMedCrossRefGoogle Scholar
  19. 19.
    Tivnan A et al (2011) MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma. BMC Cancer 11:33PubMedCrossRefGoogle Scholar
  20. 20.
    Foley NH et al (2011) MicroRNAs 10a and 10b are potent inducers of neuroblastoma cell differentiation through targeting of nuclear receptor corepressor 2. Cell Death Differ 18:1089–1098PubMedCrossRefGoogle Scholar
  21. 21.
    Griffiths-Jones S (2004) The microRNA registry. Nucleic Acids Res 32:D109–D111PubMedCrossRefGoogle Scholar
  22. 22.
    Jiang J et al (2005) Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res 33:5394–5403PubMedCrossRefGoogle Scholar
  23. 23.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408PubMedCrossRefGoogle Scholar
  24. 24.
    Cartea ME et al (2010) Phenolic compounds in Brassica vegetables. Molecules 16:251–280PubMedCrossRefGoogle Scholar
  25. 25.
    Li Y et al (2010) Regulation of microRNAs by natural agents: an emerging field in chemoprevention and chemotherapy research. Pharm Res 27:1027–1041PubMedCrossRefGoogle Scholar
  26. 26.
    Wu BT et al (2005) The apoptotic effect of green tea (−)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the Cdk2 pathway. J Agric Food Chem 53:5695–5701PubMedCrossRefGoogle Scholar
  27. 27.
    Fang M et al (2003) Tea polyphenol (−)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63:7563–7570PubMedGoogle Scholar
  28. 28.
    Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312PubMedCrossRefGoogle Scholar
  29. 29.
    Shimizu M et al (1999) Clear cell carcinoma has an expression pattern of cell cycle regulatory molecules that is unique among ovarian adenocarcinomas. Cancer 85:669–677PubMedCrossRefGoogle Scholar
  30. 30.
    Wilkinson JC et al (2004) Neutralization of Smac/Diablo by inhibitors of apoptosis (IAPs). A caspase-independent mechanism for apoptotic inhibition. J Biol Chem 279:51082–51090PubMedCrossRefGoogle Scholar
  31. 31.
    Susin SA et al (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446PubMedCrossRefGoogle Scholar
  32. 32.
    Daugas E et al (2000) Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. FEBS Lett 476:118–123PubMedCrossRefGoogle Scholar
  33. 33.
    Das A et al (2006) Mechanism of apoptosis with the involvement of calpain and caspase cascades in human malignant neuroblastoma SH-SY5Y cells exposed to flavonoids. Int J Cancer 119:2575–2585PubMedCrossRefGoogle Scholar
  34. 34.
    Karmakar S et al (2006) Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane. Neuroscience 141:1265–1280PubMedCrossRefGoogle Scholar
  35. 35.
    Karmakar S et al (2007) Combination of all-trans retinoic acid and taxol regressed glioblastoma T98G xenografts in nude mice. Apoptosis 12:2077–2087PubMedCrossRefGoogle Scholar
  36. 36.
    Ray SK et al (2000) Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC12 cells. Brain Res 852:326–334PubMedCrossRefGoogle Scholar
  37. 37.
    Mitamura S et al (1998) Cytosolic nuclease activated by caspase-3 and inhibited by DFF-45. Biochem Biophys Res Commun 243:480–484PubMedCrossRefGoogle Scholar
  38. 38.
    Sakahira H et al (1998) Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 391:96–99PubMedCrossRefGoogle Scholar
  39. 39.
    Chen Y, Stallings RL (2007) Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res 67:976–983PubMedCrossRefGoogle Scholar
  40. 40.
    Das A et al (2010) Flavonoids activated caspases for apoptosis in human glioblastoma T98G and U87MG cells but not in human normal astrocytes. Cancer 116:164–176PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Mrinmay Chakrabarti
    • 1
  • Walden Ai
    • 1
  • Naren L. Banik
    • 2
  • Swapan K. Ray
    • 1
  1. 1.Department of Pathology, Microbiology, and ImmunologyUniversity of South Carolina School of MedicineColumbiaUSA
  2. 2.Department of NeurosciencesMedical University of South CarolinaCharlestonUSA

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