Skip to main content
SpringerLink
Log in

Autophagy inhibition contributes to epigallocatechin-3-gallate-mediated apoptosis in papillary thyroid cancer cells

  • Original Article
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Background

Epigallocatechin-3-gallate is a natural polyphenolic compound that induces apoptosis in papillary thyroid cancer cells. However, its underlying molecular mechanism was not completely clarified.

Objectives

The present study demonstrated the role of apoptosis and autophagy in EGCG-treated papillary thyroid cancer cells and the relationship between these processes.

Results

EGCG significantly suppressed the viability of TPC-1 papillary thyroid cancer cells at an IC50 of 17.2 μM. EGCG induced TPC-1 cell apoptosis and cell cycle arrest at S phase and downregulated the protein expression of cyclin A and cyclin-dependent kinase-2. EGCG decreased reactive oxygen species levels, upregulated Bax expression, downregulated Bcl-2 expression and increased cytochrome C levels in the cytosol. Treatment with EGCG also increased the levels of cleaved caspase 3, cleaved caspase 9 and cleaved poly(ADP-ribose) polymerase. EGCG induced an autophagic response via the upregulation of the autophagy-related protein LC3-II and suppression of the AKT/mTOR signalling pathway. Autophagy inhibition further enhanced EGCG-induced cell apoptosis and ROS suppression, which indicated that autophagy played a cytoprotective role in EGCG-treated TPC-1 cells.

Conclusion

Taken together, these results demonstrated that autophagy inhibition was beneficial to EGCG–mediated apoptosis in papillary thyroid cancer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Ahn WS et al (2003) A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of gene expression. DNA Cell Biol 22:217–224

    Article  CAS  Google Scholar 

  • Allegri L et al (2018) Effects of nutraceuticals on anaplastic thyroid cancer cells. J Cancer Res Clin Oncol 144:285–294

    Article  CAS  Google Scholar 

  • American Thyroid Association (2009) (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167–1214

  • Choi AM, Ryter SW, Levine B (2013) Autophagy in human health and disease. N Engl J Med 368:1845–1846

    Article  CAS  Google Scholar 

  • De Amicis F et al (2013) Epigallocatechin gallate inhibits growth and epithelial-to-mesenchymal transition in human thyroid carcinoma cell lines. J Cell Physiol 228:2054–2062

    Article  Google Scholar 

  • Feng C et al (2017) Curcumin analog L48H37 induces apoptosis through ROS-mediated endoplasmic reticulum stress and STAT3 pathways in human lung cancer cells. Mol Carcinog 56:1765–1777

    Article  CAS  Google Scholar 

  • Fulda S, Kögel D (2015) Cell death by autophagy: emerging molecular mechanisms and implications for cancer therapy. Oncogene 34:5105–5113

    Article  CAS  Google Scholar 

  • Jung CH, Ro SH, Cao J, Otto NM, Kim DH (2010) mTOR regulation of autophagy. FEBS Lett 584:1287–1295

    Article  CAS  Google Scholar 

  • Kasprowska-Liśkiewicz D (2017) The cell on the edge of life and death: crosstalk between autophagy and apoptosis. Postepy Hig Med Dosw 71:825–841

    Article  Google Scholar 

  • Kenific CM, Thorburn A, Debnath J (2010) Autophagy and metastasis: another double-edged sword. Curr Opin Cell Biol 22:241–245

    Article  CAS  Google Scholar 

  • Khan N, Mukhtar H (2018) Tea Polyphenols in Promotion of Human Health. Nutrients 11:39

    Article  Google Scholar 

  • Lim YC, Cha YY (2011) Epigallocatechin-3-gallate induces growth inhibition and apoptosis of human anaplastic thyroid carcinoma cells through suppression of EGFR/ERK pathway and cyclin B1/CDK1 complex. J Surg Oncol 104:776–780

    Article  CAS  Google Scholar 

  • Link A, Balaguer F, Goel A (2010) Cancer chemoprevention by dietary polyphenols: promising role for epigenetics. Biochem Pharmacol 80:1771–1792

    Article  CAS  Google Scholar 

  • Liou GY, Storz P (2010) Reactive oxygen species in cancer. Free Radic Res 44:479–496

    Article  CAS  Google Scholar 

  • Ma S, Wang C, Bai J, Wang X, Li C (2015) Association of tea consumption and the risk of thyroid cancer: a meta-analysis. Int J Clin Exp Med 8:14345–14351

    PubMed  PubMed Central  Google Scholar 

  • Mizushima N, Yoshimori T, Levine B (2010) Methods in mammalian autophagy research. Cell 140:313–326

    Article  CAS  Google Scholar 

  • Mukhtar E, Adhami VM, Khan N, Mukhtar H (2012) Apoptosis and autophagy induction as mechanism of cancer prevention by naturally occurring dietary agents. Curr Drug Targets 13:1831–1841

    Article  CAS  Google Scholar 

  • Pan MH, Ghai G, Ho CT (2008) Food bioactives, apoptosis, and cancer. Mol Nutr Food Res 52:43–52

    Article  CAS  Google Scholar 

  • Sawka AM et al (2004) Clinical review 170: A systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer. J Clin Endocrinol Metab 89:3668–3676

    Article  CAS  Google Scholar 

  • Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8:579–591

    Article  CAS  Google Scholar 

  • Tumino D, Frasca F, Newbold K (2017) Updates on the management of advanced, metastatic, and radioiodine refractory differentiated thyroid cancer. Front Endocrinol 8:312

    Article  Google Scholar 

  • Wang SI, Mukhtar H (2002) Gene expression profile in human prostate LNCaP cancer cells by (–) epigallocatechin-3-gallate. Cancer Lett 182:43–45

    Article  CAS  Google Scholar 

  • Wang TS, Sosa JA (2018) Thyroid surgery for differentiated thyroid cancer—recent advances and future directions. Nat Rev Endocrinol 14:670–683

    Article  CAS  Google Scholar 

  • Wang W, Yang Y, Zhang W, Wu W (2014) Association of tea consumption and the risk of oral cancer: a meta-analysis. Oral Oncol 50:276–281

    Article  Google Scholar 

  • Wu D et al (2019) Epigallocatechin-3-gallate inhibits the growth and increases the apoptosis of human thyroid carcinoma cells through suppression of EGFR/RAS/RAF/MEK/ERK signaling pathway. Cancer Cell Int 19:43

    Article  Google Scholar 

  • Yi H et al (2014) Autophagy: A potential target for thyroid cancer therapy (Review). Mol Clin Oncol 2:661–665

    Article  Google Scholar 

  • Zhang Y et al (2012) (-)-Epigallocatechin-3-gallate induces non-apoptotic cell death in human cancer cells via ROS-mediated lysosomal membrane permeabilization. PLoS ONE 7:e46749

    Article  CAS  Google Scholar 

  • Zhao T et al (2017) Rosbin, a synthetic small molecule, induces A549 cells apoptosis through a ROS-mediated pathway. Cell Biol Int 41:221–226

    Article  CAS  Google Scholar 

  • Zheng X et al (2018) Correlation of Reactive Oxygen Species Levels with Resveratrol Sensitivities of Anaplastic Thyroid Cancer Cells. Oxid Med Cell Longev 6235417

Download references

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant Number 81370889).

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, 212001, China

    Ling Bu, Tingting Zheng, Chaoming Mao, Xiao Mou, Chengcheng Xu, Xuan Luo, Qingyan Lu, Liyang Dong & Xuefeng Wang

  2. Department of Pharmacy, Jiangsu Health Vocational College, 69 Huangshanling Road, Nanjing, 211800, China

    Ling Bu

  3. Department of Nuclear Medicine, The First People’s Hospital of Yancheng, 166 Yulong west Road, Yancheng, 224005, China

    Fei Wu

Authors
  1. Ling Bu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tingting Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chaoming Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao Mou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chengcheng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xuan Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qingyan Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Liyang Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xuefeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Chaoming Mao, Ling Bu and Tingting Zheng were responsible for the conception and design of the study, for analysis and interpretation of data and for drafting and revising the manuscript. Fei Wu, Xiao Mou, Chengcheng Xu, Xuan Luo and Qingyan Lu were responsible for the conception and design of the study, data acquisition, interpretation of data and review of the manuscript. Liyang Dong and Xuefeng Wang were responsible for the conception and design of the study, for data acquisition and for reviewing the manuscript. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Chaoming Mao.

Ethics declarations

Conflict of interest

Ling Bu declares she has no conflict of interest. Tingting Zheng declares she has no conflict of interest. Chaoming Mao declares he has no conflict of interest. Fei Wu declares she has no conflict of interest. Xiao Mou declares she has no conflict of interest. Chengcheng Xu declares she has no conflict of interest. Xuan Luo declares she has no conflict of interest. Qingyan Lu declares she has no conflict of interest. Liyang Dong declares he has no conflict of interest. Xuefeng Wang declares she has no conflict of interest.

Ethics statement

The study includes only laboratory studies on a stable established cell line. No ethical or institutional approval was required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bu, L., Zheng, T., Mao, C. et al. Autophagy inhibition contributes to epigallocatechin-3-gallate-mediated apoptosis in papillary thyroid cancer cells. Mol. Cell. Toxicol. 17, 533–542 (2021). https://doi.org/10.1007/s13273-021-00164-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-021-00164-3

Keywords

Search

Navigation