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Synergistic enhancement of anticancer effects on numerous human cancer cell lines treated with the combination of EGCG, other green tea catechins, and anticancer compounds

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  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

In 2008, we reported that 10 Japanese-size cups of green tea daily, supplemented with tablets of green tea extract (GTE), reduced the recurrence of colorectal adenoma by 51.6 % in patients after polypectomy. Based on these results, we paid special attention to Japanese cancer patients, who consume green tea every day and are administered anticancer drugs. This encouraged us to study whether the combination of green tea catechins and anticancer drugs has the potential to enhance the efficacy of the drugs.

Results and discussion

The combination of GTE and NSAIDs synergistically inhibited tumor development in rodents through the activation of the GADD153–DR5–TRAIL apoptotic pathway. Since then, this study was further extended by various investigators to the combinations of EGCG and other green tea catechins with anticancer compounds, the latter of which include NSAIDs, phytochemicals, and anticancer drugs. In order to demonstrate whether diversity of the combinations would generally induce synergistic anticancer effects on numerous human cancer cell lines, we studied the results of 42 in vitro combination experiments and the synergistic inhibition of tumor volume of 13 combination experiments using xenograft mouse models, which were previously reported by other investigators. The various combinations of EGCG and anticancer compounds induced similar synergistic anticancer effects for both in vitro and in vivo experiments, and showed an average reduction in tumor volume by 70.3 %. Considering the evidence showing that treatment with EGCG inhibited self-renewal of cancer stem cells, the combination shows a great advantage.

Conclusion

Green tea is a cancer preventive for humans, showing a new trend of green tea catechins as synergists with anticancer compounds.

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Abbreviations

EGCG:

(−)-Epigallocatechin gallate

ER:

Estrogen receptor

GADD153 :

Growth arrest and DNA damage-inducible gene 153

GTE:

Green tea extract

HDAC:

Histone deacetylase

NSAIDs:

Nonsteroidal anti-inflammatory drugs

TRAIL:

TNF-related apoptosis-inducing ligand

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Acknowledgments

We thank Drs. Kei Nakachi and Kazue Imai at Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima; Drs. Masahito Shimizu and Hisataka Moriwaki at Department of Medicine, Gifu University; and Mrs. Yoshiaki Kitaoka, Kenta Nakajima, and Dr. Atsushi Takahashi at the Green Tea Laboratory of Saitama Prefectural Agriculture and Forestry Research Center, for their fruitful collaborations and stimulating discussion; and Mrs. Ikuko Shiotani at the Saitama Cancer Center Hospital for her generous collaborations.

Conflict of interest

Here, we declare that we have no conflicts of interest.

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Authors and Affiliations

  1. Department of Clinical Laboratory Medicine, Faculty of Medicine, Saga University, Nabeshima, Saga, 849-8501, Japan

    Hirota Fujiki, Eisaburo Sueoka & Tatsuro Watanabe

  2. Graduate School of Science and Engineering, Saitama University, Sakuraku, Saitama, 338-8570, Japan

    Masami Suganuma

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  1. Hirota Fujiki
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  2. Eisaburo Sueoka
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  3. Tatsuro Watanabe
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  4. Masami Suganuma
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Correspondence to Hirota Fujiki.

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Fujiki, H., Sueoka, E., Watanabe, T. et al. Synergistic enhancement of anticancer effects on numerous human cancer cell lines treated with the combination of EGCG, other green tea catechins, and anticancer compounds. J Cancer Res Clin Oncol 141, 1511–1522 (2015). https://doi.org/10.1007/s00432-014-1899-5

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