Tumor Biology

, Volume 36, Issue 4, pp 2747–2761 | Cite as

(-)-Epigallocatechin-3-gallate inhibits nasopharyngeal cancer stem cell self-renewal and migration and reverses the epithelial–mesenchymal transition via NF-κB p65 inactivation

  • Ya-Jun Li
  • Shun-Long Wu
  • Song-Mei Lu
  • Fang Chen
  • Ying Guo
  • Sheng-Min Gan
  • Yan-Long Shi
  • Shuang Liu
  • Shao-Lin Li
Research Article

Abstract

The cancer stem cell (CSC) theory states that many types of cancer, including nasopharyngeal cancer (NPC), are initiated from and maintained by CSCs, which may be responsible for tumor relapse and resistance to therapy. It is imperative that nasopharyngeal cancer stem cells (NPCSCs) be specifically targeted to eradicate NPC and prevent recurrence. Epigallocatechin-3-gallate (EGCG) inhibits cancer progression by attenuating NF-κB p65 activity, which is upregulated in CSCs and plays an important role in epithelial–mesenchymal transition (EMT). The purpose of this study is to confirm the self-renewal and migration inhibitory effects of EGCG toward NPCSCs and to clarify its mechanism of activity. We enriched and characterized NPCSCs by collecting spheroid-derived cells grown in serum-free medium (SFM) and examined the effects of EGCG on the characteristics of NPCSCs and studied the underlying mechanisms using soft agar colony assays, transwell migration assays, reverse transcriptase polymerase chain reaction (RT-PCR), Western blot analysis, immunofluorescence staining, and xenograft studies. NPC spheroids enriched from NPC cell lines acquired CSC traits and underwent EMT. EGCG inhibited the NPCSCs’ self-renewal and migration and reversed EMT, and combined treatment with EGCG and cisplatin reduced the growth of CSC tumor xenografts. Moreover, EGCG inhibited NF-κB p65 activity by modulating the cellular localization of p65 and decreasing the transcriptional regulation of NF-κB p65 on Twist1 expression. NF-κB p65 is a novel therapeutic target in NPCSCs, and the inhibition of activated NF-κB p65 in CSCs by EGCG may offer an effective treatment for NPC.

Keywords

Nasopharyngeal cancer Cancer stem cells Epigallocatechin-3-gallate Epithelial–mesenchymal transition Self-renewal and migration NF-κB p65 

Abbreviations

CSC

Cancer stem cell

NPC

Nasopharyngeal cancer

NPCSCs

Nasopharyngeal cancer stem cells

SC

Spheroid cell

EMT

Epithelial–mesenchymal transition

EGCG

Epigallocatechin-3-gallate

SFM

Serum-free medium

NF-κB

Nuclear factor κB

RT-PCR

Quantitative reverse transcriptase polymerase chain reaction

DMSO

Dimethylsulfoxide

FACS

Fluorescence-activated cell sorting

FBS

Fetal bovine serum

EGF

Epidermal growth factor

bFGF

Human recombinant basic fibroblast growth factor

DMEM/F12

Dulbecco’s modified Eagle’s medium F12

Notes

Acknowledgments

This research is supported by the General Program of the National Natural Science Foundation of China (No. 81171365).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ya-Jun Li
    • 1
  • Shun-Long Wu
    • 1
  • Song-Mei Lu
    • 1
  • Fang Chen
    • 2
  • Ying Guo
    • 3
  • Sheng-Min Gan
    • 1
  • Yan-Long Shi
    • 1
  • Shuang Liu
    • 1
  • Shao-Lin Li
    • 1
  1. 1.Department of Radiology, College of Basic MedicineChongqing Medical UniversityChongqingChina
  2. 2.Department of OncologyAffiliated Hospital of Zunyi Medical CollegeZunyiChina
  3. 3.Department of OncologyAffiliated Hospital of Luzhou Medical CollegeLuzhouChina

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