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Endocrine

pp 1–11 | Cite as

Evodiamine in combination with histone deacetylase inhibitors has synergistic cytotoxicity in thyroid carcinoma cells

  • Si Hyoung Kim
  • Jun Goo Kang
  • Chul Sik Kim
  • Sung-Hee Ihm
  • Moon Gi Choi
  • Seong Jin LeeEmail author
Original Article
  • 8 Downloads

Abstract

Purpose

The impact of evodiamine in combination with histone deacetylase (HDAC) inhibitors on survival of thyroid carcinoma cells was identified.

Methods

TPC-1 and SW1736 human thyroid carcinoma cells were used.

Results

After treatment with evodiamine and PXD101, cell viability, the percentage of viable cells and Bcl2 protein levels decreased, whereas cytotoxic activity, the percentage of apoptotic cells, the protein levels of γH2AX, acetyl. histone H3 and cleaved PARP, and reactive oxygen species (ROS) production increased. In cells treated with both evodiamine and PXD101, compared with PXD101 alone, decrement of cell viability, the percentage of viable cells, and Bcl2 protein levels as well as increment of cytotoxic activity, the percentage of apoptotic cells, the protein levels of γH2AX and cleaved PARP, and ROS production were significant, causing decrement of Bcl2/Bax ratio. Furthermore, all of the combination index values were <1.0, suggesting synergistic cytotoxicity of two agents. Wortmannin decreased cell viability and the percentage of viable cells, whereas it increased cytotoxic activity and the percentage of apoptotic cells without alteration in ROS production. The changes in cells treated with both evodiamine and suberoylanilide hydroxamic acid or trichostatin A were similar to those in cells treated with both evodiamine and PXD101.

Conclusions

Our results demonstrate that evodiamine synergizes with HDAC inhibitors in inducing cytotoxic activities by involving survival-related proteins and ROS in thyroid carcinoma cells. Moreover, repression of PI3K/Akt signaling synergistically reinforces cytotoxicity of evodiamine combined with HDAC inhibitors in thyroid carcinoma cells.

Keywords

Thyroid carcinoma Evodiamine HDAC inhibitor Synergism Akt 

Abbreviations

ATC

anaplastic thyroid carcinoma

CI

combination index

DMSO

dimethylsulfoxide

ED50

the concentrations of each drug required for 50% inhibition

FTC

follicular thyroid cancer

HDAC

histone deacetylase

PARP

poly (ADP-ribose) polymerase

PTC

papillary thyroid cancer

γH2AX

phospho-histone H2A.X

ROS

reactive oxygen species

SAHA

suberoylanilide hydroxamic acid

TSA

trichostatin A.

Notes

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2018R1D1A1B07044901) to S.J.L.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12020_2019_1885_MOESM1_ESM.pptx (396 kb)
Supplemental figures

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Si Hyoung Kim
    • 1
  • Jun Goo Kang
    • 1
  • Chul Sik Kim
    • 1
  • Sung-Hee Ihm
    • 1
  • Moon Gi Choi
    • 1
  • Seong Jin Lee
    • 1
    Email author
  1. 1.Division of Endocrinology and Metabolism, Department of Internal Medicine, College of MedicineHallym UniversityChuncheonRepublic of Korea

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