Extracellular signal‑regulated kinase inhibition is required for methanol extract of Smilax china L.‑induced apoptosis through death receptor 5 in human oral mucoepidermoid carcinoma cells

Yu,Hyun‑Ju; Shin,Ji‑Ae; Lee,Syng‑Ook; Kwon,Ki  Han; Cho,Sung‑Dae

doi:10.3892/mmr.2013.1826

Extracellular signal‑regulated kinase inhibition is required for methanol extract of Smilax china L.‑induced apoptosis through death receptor 5 in human oral mucoepidermoid carcinoma cells

Authors:
- Hyun‑Ju Yu
- Ji‑Ae Shin
- Syng‑Ook Lee
- Ki Han Kwon
- Sung‑Dae Cho
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Affiliations: Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, North Jeolla 561‑756, Republic of Korea, Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA, Department of Food Science and Nutrition, College of Health, Welfare and Education, Gwangju University, Gwangju 503‑703, Republic of Korea
Published online on: November 22, 2013 https://doi.org/10.3892/mmr.2013.1826
Pages: 663-668

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Abstract

Smilax china L., a well‑known Chinese traditional medicine, has been used as an anti‑inflammatory, anti‑cancer and analgesic agent, but its role has not yet been fully elucidated in oral mucoepidermoid carcinoma (MEC). The present study focused on addressing the anticancer activity and molecular mechanism of methanol extract of Smilax china L. (MESC) in MC‑3 human oral MEC cells. The results indicated that MESC inhibited cell growth and induced apoptosis in MC‑3 cells. These observations were found to correlate with increases in truncated BH3 interacting‑domain death agonist and B‑cell lymphoma 2 (Bcl‑2) interacting mediator of cell death, but not Bcl‑2 homologous antagonist killer, Bcl‑2‑associated X protein, Bcl‑2, B‑cell lymphoma‑extra large and induced myeloid leukemia cell differentiation protein levels. MESC also damaged the mitochondrial membrane potential, cleaved caspase‑8 protein and increased death receptor 5 (DR5) protein levels by enhancing the stability of DR5 protein. Furthermore, MESC affected the phosphorylation of extracellular signal‑regulated kinase (ERK) only, and did not affect c‑Jun N‑terminal kinase or p38 phosphorylation. Co‑treatment with MESC and an ERK inhibitor (PD98059) significantly increased the expression of DR5 to induce apoptosis in MC‑3 cells. Therefore, these results suggest that MESC may induce apoptosis via the ERK pathway and may be a potential anticancer drug candidate against human oral MEC.

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