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Cellular Oncology

, Volume 40, Issue 3, pp 235–246 | Cite as

Silymarin and its active component silibinin act as novel therapeutic alternatives for salivary gland cancer by targeting the ERK1/2-Bim signaling cascade

  • Eun-Sun Choi
  • Sejun Oh
  • Boonsil Jang
  • Hyun-Ju Yu
  • Ji-Ae Shin
  • Nam-Pyo Cho
  • In-Hyoung Yang
  • Dong-Hoon Won
  • Hye-Jeong Kwon
  • Seong Doo Hong
  • Sung-Dae ChoEmail author
Original Paper

Abstract

Purpose

Approximately 20% of all salivary gland cancer patients who are treated with current treatment modalities will ultimately develop metastases. Its most common form, mucoepidermoid carcinoma (MEC) is a highly aggressive tumor with an overall 5-year survival rate of ~30%. Until now, several chemotherapeutic drugs have been tested for the treatment of salivary gland tumors, but the results have been disappointing and the drugs often cause unwanted side effects. Therefore, several recent studies have focused on the potential of alternative and/or complementary therapeutic options, including the use of silymarin.

Methods

The effects of silymarin and its active component silibinin on salivary gland cancer-derived MC3 and HN22 cells and their underlying molecular mechanisms were examined using trypan blue exclusion, 4′-6-diamidino-2-phenylindole (DAPI) staining, Live/Dead, Annexin V/PI staining, mitochondrial membrane potential (ΔΨm) measurement, quantitative RT-PCR, soft agar colony formation and Western blotting analyses.

Results

We found that silymarin and silibinin dramatically increased the expression of the pro-apoptotic protein Bim in a concentration- and time-dependent manner and, concomitantly, induced apoptosis in MC3 and HN22 cells. We also found that ERK1/2 signaling inhibition successfully sensitized these cells to the apoptotic effects of silymarin and silibinin, which indicates that the ERK1/2 signaling pathway may act as an upstream regulator that modulates the silymarin/silibinin-induced Bim signaling pathway.

Conclusions

Taken together, we conclude that ERK1/2 signaling pathway inhibition by silymarin and silibinin increases the expression of the pro-apoptotic Bcl-2 family member Bim which, subsequently, induces mitochondria-mediated apoptosis in salivary gland cancer-derived cells.

Keywords

Silymarin Silibinin Salivary gland tumor Apoptosis ERK/Bim signaling 

Notes

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014R1A1A2055874 and 2016R1A2B4006794).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

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Copyright information

© International Society for Cellular Oncology 2017

Authors and Affiliations

  • Eun-Sun Choi
    • 1
  • Sejun Oh
    • 2
  • Boonsil Jang
    • 2
  • Hyun-Ju Yu
    • 2
  • Ji-Ae Shin
    • 3
  • Nam-Pyo Cho
    • 2
  • In-Hyoung Yang
    • 2
  • Dong-Hoon Won
    • 3
  • Hye-Jeong Kwon
    • 3
  • Seong Doo Hong
    • 3
  • Sung-Dae Cho
    • 3
    Email author
  1. 1.Division of high-risk pathogen researchKorea Centers for Disease Control and PreventionOsongRepublic of Korea
  2. 2.Department of Oral Pathology, School of Dentistry and Institute of Biodegradable material, Institute of Oral BioscienceChonbuk National UniversityJeonjuRepublic of Korea
  3. 3.Department of Oral Pathology, School of Dentistry and Dental Research InstituteSeoul National UniversitySeoulRepublic of Korea

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