Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines

Chien-Hung Lin, Yao-An Shen, Peir-Haur Hung, Yuan-Bin Yu, Yann-Jang Chen

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

BACKGROUND: Previous studies have demonstrated that the consumption of green tea inhibits the growth of various cancers. Most cancers are believed to be initiated from and maintained by a small population of cancer stem-like cells (CSC) or tumor-initiating cells (TIC) that are responsible for tumor relapse and chemotherapeutic resistance. Although epigallocathechin gallate (EGCG), the most abundant catechin in green tea, has been reported to induce growth inhibition and apoptosis in some cancer cells, its effect on CSC is undefined. In this study, we enriched CSC by the sphere formation, and provided an efficient model for further experiments. Using this method, we examined the effects of EGCG regulating the nasopharyngeal carcinoma (NPC) CSC and attempted to elucidate the possible mechanisms.

METHODS: NPC TW01 and TW06 cell lines were enriched by sphere formation and characterized their phenotypical properties, such as invasion capacity, epithelial-mesenchymal transition (EMT) and gene expression were analyzed by quantitative real-time reverse transcription polymerase chain reaction (q-RT-PCR). EGCG-induced growth inhibition in the parental and sphere-derived cells was determined by MTT and bromodeoxyuridine (BrdU) assay. EGCG-induced apoptosis was analyzed by flow cytometry with Annexin V and PI staining. The effects of EGCG on sphere-derived cell tumorigenicity, migration and invasion were determined by soft agar assay, wound healing, and cell invasion assay. The alternation of protein expression regulated by EGCG on these sphere-derived cells was assessed by immunofluorescence staining and western blot.

RESULTS: NPC sphere-derived cells grown in serum-free non-adherent culture showed increased expression of stem cell markers and EMT markers compared to parental cells grown in conventional culture. Although EGCG induced growth inhibition and apoptosis in the parental cells in a dose-dependent manner, it was not as effective against spheres. However, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures.

CONCLUSIONS: Overall, these findings show that NPC cells with sphere formations possess the properties of CSC. Using this model, we found that EGCG regulated NPC CSC, their self-renewal capacity, and inhibited their invasive characteristics. It supports the pivotal role of EGCG as a dietary compound targeting NPC and may decrease recurrence and metastasis in nasopharyngeal carcinoma cells.

Original languageEnglish
Pages (from-to)201
JournalBMC Complementary and Alternative Medicine
Volume12
DOIs
Publication statusPublished - Oct 30 2012
Externally publishedYes

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Nasopharyngeal Neoplasms
Epithelial-Mesenchymal Transition
Polyphenols
Tea
Neoplastic Stem Cells
Cell Line
Apoptosis
Growth
Neoplasms
Stem Cells
Staining and Labeling
Recurrence
Nasopharyngeal carcinoma
Catechin
Annexin A5
Bromodeoxyuridine
Wound Healing
Reverse Transcription
Agar
Cell Movement

Keywords

  • Antineoplastic Agents, Phytogenic/pharmacology
  • Camellia sinensis/chemistry
  • Carcinoma/drug therapy
  • Catechin/analogs & derivatives
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition/drug effects
  • Humans
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms/drug therapy
  • Neoplastic Stem Cells/drug effects
  • Phytotherapy
  • Plant Extracts/pharmacology
  • Polyphenols/pharmacology
  • Tea

Cite this

Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines. / Lin, Chien-Hung; Shen, Yao-An; Hung, Peir-Haur; Yu, Yuan-Bin; Chen, Yann-Jang.

In: BMC Complementary and Alternative Medicine, Vol. 12, 30.10.2012, p. 201.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: Previous studies have demonstrated that the consumption of green tea inhibits the growth of various cancers. Most cancers are believed to be initiated from and maintained by a small population of cancer stem-like cells (CSC) or tumor-initiating cells (TIC) that are responsible for tumor relapse and chemotherapeutic resistance. Although epigallocathechin gallate (EGCG), the most abundant catechin in green tea, has been reported to induce growth inhibition and apoptosis in some cancer cells, its effect on CSC is undefined. In this study, we enriched CSC by the sphere formation, and provided an efficient model for further experiments. Using this method, we examined the effects of EGCG regulating the nasopharyngeal carcinoma (NPC) CSC and attempted to elucidate the possible mechanisms.METHODS: NPC TW01 and TW06 cell lines were enriched by sphere formation and characterized their phenotypical properties, such as invasion capacity, epithelial-mesenchymal transition (EMT) and gene expression were analyzed by quantitative real-time reverse transcription polymerase chain reaction (q-RT-PCR). EGCG-induced growth inhibition in the parental and sphere-derived cells was determined by MTT and bromodeoxyuridine (BrdU) assay. EGCG-induced apoptosis was analyzed by flow cytometry with Annexin V and PI staining. The effects of EGCG on sphere-derived cell tumorigenicity, migration and invasion were determined by soft agar assay, wound healing, and cell invasion assay. The alternation of protein expression regulated by EGCG on these sphere-derived cells was assessed by immunofluorescence staining and western blot.RESULTS: NPC sphere-derived cells grown in serum-free non-adherent culture showed increased expression of stem cell markers and EMT markers compared to parental cells grown in conventional culture. Although EGCG induced growth inhibition and apoptosis in the parental cells in a dose-dependent manner, it was not as effective against spheres. However, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures.CONCLUSIONS: Overall, these findings show that NPC cells with sphere formations possess the properties of CSC. Using this model, we found that EGCG regulated NPC CSC, their self-renewal capacity, and inhibited their invasive characteristics. It supports the pivotal role of EGCG as a dietary compound targeting NPC and may decrease recurrence and metastasis in nasopharyngeal carcinoma cells.",
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T1 - Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines

AU - Lin, Chien-Hung

AU - Shen, Yao-An

AU - Hung, Peir-Haur

AU - Yu, Yuan-Bin

AU - Chen, Yann-Jang

PY - 2012/10/30

Y1 - 2012/10/30

N2 - BACKGROUND: Previous studies have demonstrated that the consumption of green tea inhibits the growth of various cancers. Most cancers are believed to be initiated from and maintained by a small population of cancer stem-like cells (CSC) or tumor-initiating cells (TIC) that are responsible for tumor relapse and chemotherapeutic resistance. Although epigallocathechin gallate (EGCG), the most abundant catechin in green tea, has been reported to induce growth inhibition and apoptosis in some cancer cells, its effect on CSC is undefined. In this study, we enriched CSC by the sphere formation, and provided an efficient model for further experiments. Using this method, we examined the effects of EGCG regulating the nasopharyngeal carcinoma (NPC) CSC and attempted to elucidate the possible mechanisms.METHODS: NPC TW01 and TW06 cell lines were enriched by sphere formation and characterized their phenotypical properties, such as invasion capacity, epithelial-mesenchymal transition (EMT) and gene expression were analyzed by quantitative real-time reverse transcription polymerase chain reaction (q-RT-PCR). EGCG-induced growth inhibition in the parental and sphere-derived cells was determined by MTT and bromodeoxyuridine (BrdU) assay. EGCG-induced apoptosis was analyzed by flow cytometry with Annexin V and PI staining. The effects of EGCG on sphere-derived cell tumorigenicity, migration and invasion were determined by soft agar assay, wound healing, and cell invasion assay. The alternation of protein expression regulated by EGCG on these sphere-derived cells was assessed by immunofluorescence staining and western blot.RESULTS: NPC sphere-derived cells grown in serum-free non-adherent culture showed increased expression of stem cell markers and EMT markers compared to parental cells grown in conventional culture. Although EGCG induced growth inhibition and apoptosis in the parental cells in a dose-dependent manner, it was not as effective against spheres. However, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures.CONCLUSIONS: Overall, these findings show that NPC cells with sphere formations possess the properties of CSC. Using this model, we found that EGCG regulated NPC CSC, their self-renewal capacity, and inhibited their invasive characteristics. It supports the pivotal role of EGCG as a dietary compound targeting NPC and may decrease recurrence and metastasis in nasopharyngeal carcinoma cells.

AB - BACKGROUND: Previous studies have demonstrated that the consumption of green tea inhibits the growth of various cancers. Most cancers are believed to be initiated from and maintained by a small population of cancer stem-like cells (CSC) or tumor-initiating cells (TIC) that are responsible for tumor relapse and chemotherapeutic resistance. Although epigallocathechin gallate (EGCG), the most abundant catechin in green tea, has been reported to induce growth inhibition and apoptosis in some cancer cells, its effect on CSC is undefined. In this study, we enriched CSC by the sphere formation, and provided an efficient model for further experiments. Using this method, we examined the effects of EGCG regulating the nasopharyngeal carcinoma (NPC) CSC and attempted to elucidate the possible mechanisms.METHODS: NPC TW01 and TW06 cell lines were enriched by sphere formation and characterized their phenotypical properties, such as invasion capacity, epithelial-mesenchymal transition (EMT) and gene expression were analyzed by quantitative real-time reverse transcription polymerase chain reaction (q-RT-PCR). EGCG-induced growth inhibition in the parental and sphere-derived cells was determined by MTT and bromodeoxyuridine (BrdU) assay. EGCG-induced apoptosis was analyzed by flow cytometry with Annexin V and PI staining. The effects of EGCG on sphere-derived cell tumorigenicity, migration and invasion were determined by soft agar assay, wound healing, and cell invasion assay. The alternation of protein expression regulated by EGCG on these sphere-derived cells was assessed by immunofluorescence staining and western blot.RESULTS: NPC sphere-derived cells grown in serum-free non-adherent culture showed increased expression of stem cell markers and EMT markers compared to parental cells grown in conventional culture. Although EGCG induced growth inhibition and apoptosis in the parental cells in a dose-dependent manner, it was not as effective against spheres. However, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures.CONCLUSIONS: Overall, these findings show that NPC cells with sphere formations possess the properties of CSC. Using this model, we found that EGCG regulated NPC CSC, their self-renewal capacity, and inhibited their invasive characteristics. It supports the pivotal role of EGCG as a dietary compound targeting NPC and may decrease recurrence and metastasis in nasopharyngeal carcinoma cells.

KW - Antineoplastic Agents, Phytogenic/pharmacology

KW - Camellia sinensis/chemistry

KW - Carcinoma/drug therapy

KW - Catechin/analogs & derivatives

KW - Cell Line, Tumor

KW - Epithelial-Mesenchymal Transition/drug effects

KW - Humans

KW - Nasopharyngeal Carcinoma

KW - Nasopharyngeal Neoplasms/drug therapy

KW - Neoplastic Stem Cells/drug effects

KW - Phytotherapy

KW - Plant Extracts/pharmacology

KW - Polyphenols/pharmacology

KW - Tea

U2 - 10.1186/1472-6882-12-201

DO - 10.1186/1472-6882-12-201

M3 - Article

C2 - 23110507

VL - 12

SP - 201

JO - BMC Complementary and Alternative Medicine

JF - BMC Complementary and Alternative Medicine

SN - 1472-6882

ER -