Silymarin and Its Active Component Silibinin Act As Novel Therapeutic Alternatives for Salivary Gland Cancer by Targeting the ERK1/2-Bim Signaling Cascade

Overview

Journal Cell Oncol (Dordr)

Publisher Springer

Date 2017 Apr 13

PMID 28401485

Citations 12

Authors

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 Cho

Affiliations

Soon will be listed here.

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.

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