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

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.

• Authors: Ya-Jun Li, Shun-Long Wu, Song-Mei Lu, Fang Chen, Ying Guo, Sheng-Min Gan, Yan-Long Shi, Shuang Liu, Shao-Lin Li
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 4 Pg. 2747-61 (Apr 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25487615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• HSAJ2425 protein, human
• Intracellular Signaling Peptides and Proteins
• NF-kappa B
• Neoplasm Proteins
• Catechin
• epigallocatechin gallate

Topics

• Carrier Proteins (antagonists & inhibitors, genetics)
• Catechin (administration & dosage, analogs & derivatives)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Epithelial-Mesenchymal Transition
• Humans
• Intracellular Signaling Peptides and Proteins
• NF-kappa B (genetics)
• Nasopharyngeal Neoplasms (drug therapy, genetics, pathology)
• Neoplasm Proteins (antagonists & inhibitors, genetics)
• Neoplastic Stem Cells (drug effects)
• Signal Transduction (drug effects)