Open Access

Combination of resveratrol and green tea epigallocatechin gallate induces synergistic apoptosis and inhibits tumor growth in vivo in head and neck cancer models

  • Authors:
    • A.R.M. Ruhul Amin
    • Dongsheng Wang
    • Sreenivas Nannapaneni
    • Rajan Lamichhane
    • Zhuo Georgia Chen
    • Dong M. Shin
  • View Affiliations

  • Published online on: March 31, 2021     https://doi.org/10.3892/or.2021.8038
  • Article Number: 87
  • Copyright: © Amin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Despite widespread interest in chemoprevention and therapy due to the high margin of safety of dietary natural compounds, clinical intervention with single agents has failed to yield the expected outcomes, mostly due to poor bioavailability and low potency. Combinations of natural agents with synergistic effects are gaining increasing attention. In the present study, in vitro and in vivo antitumor effects of a combination of two natural dietary agents, green tea epigallocatechin gallate (EGCG) and resveratrol were investigated. It was revealed that their combination at low doses (at which single agents induce minimal apoptosis) synergistically increased apoptosis (combination index <1) in head and neck cancer cell lines. Synergistic apoptosis was also supported by caspase‑3 and PARP cleavage. The combination also significantly inhibited growth of xenografted head and neck tumors in nude mice as supported by significant inhibition of tumor volume, tumor weight and Ki67 expression, and increase in TUNEL‑positive cells. Mechanistic studies revealed that the combination inhibited AKT‑mTOR signaling both in vitro and in vivo. In addition, overexpression of constitutively active AKT protected cells from apoptosis induced by the combination of EGCG and resveratrol. Collectively, the present results for the first time suggest that the combination of EGCG and resveratrol has synergistic growth inhibitory effects and provide an important rationale for future clinical development for chemoprevention and treatment of head and neck cancer.
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May-2021
Volume 45 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Amin AR, Wang D, Nannapaneni S, Lamichhane R, Chen ZG and Shin DM: Combination of resveratrol and green tea epigallocatechin gallate induces synergistic apoptosis and inhibits tumor growth <em>in vivo</em> in head and neck cancer models. Oncol Rep 45: 87, 2021
APA
Amin, A.R., Wang, D., Nannapaneni, S., Lamichhane, R., Chen, Z.G., & Shin, D.M. (2021). Combination of resveratrol and green tea epigallocatechin gallate induces synergistic apoptosis and inhibits tumor growth <em>in vivo</em> in head and neck cancer models. Oncology Reports, 45, 87. https://doi.org/10.3892/or.2021.8038
MLA
Amin, A. R., Wang, D., Nannapaneni, S., Lamichhane, R., Chen, Z. G., Shin, D. M."Combination of resveratrol and green tea epigallocatechin gallate induces synergistic apoptosis and inhibits tumor growth <em>in vivo</em> in head and neck cancer models". Oncology Reports 45.5 (2021): 87.
Chicago
Amin, A. R., Wang, D., Nannapaneni, S., Lamichhane, R., Chen, Z. G., Shin, D. M."Combination of resveratrol and green tea epigallocatechin gallate induces synergistic apoptosis and inhibits tumor growth <em>in vivo</em> in head and neck cancer models". Oncology Reports 45, no. 5 (2021): 87. https://doi.org/10.3892/or.2021.8038