Schizandra chinensis extracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

作者：Kim Hyun Sul; Lee Jae Hwa; Park Hyun Soo; Lee Geum San; Kim Hyung Woo; Ha Ki Tae^*; Kim Byung Joo

来源：Pharmaceutical Biology, 2015, 53(2): 212-219.

DOI：10.3109/13880209.2014.913297

• AGS cell
• apoptosis
• gastric cancer
• Schizandra chinensis fruit extract

Context: Schizandra chinensis Baill (Magnoliaceae) fruit extract (SCE) is considered a traditional herbal medicine for the treatment and alleviation of various diseases. Gastric cancer is the second most common cause of cancer-related death worldwide, and the first most common in Korea.
Objectives: This study investigates the mechanism of SCE-induced apoptosis in AGS human gastric cancer cells.
Materials and methods: SCE concentrations from 100 to 400 mg/ml were used. Cell viabilities were determined using MTT assay. Members of the Bcl-2 family and Bax were detected by Western blotting. RT-PCR was performed to measure the expression level of the Fas/FasL pro-apoptotic genes.
Results: SCE inhibited the proliferation AGS cells for 24 or 72 h (inhibition by 3.1% +/- 5.2% at 100 mu g/ml and 87.3% +/- 7.6% at 400 mu g/ml at 24 h and by 40.2% +/- 5.3% 100 mu g/ml and 95.3% +/- 1.3% 400 mu g/ml at 72 h) and increased the sub-G1 phase (25.3% +/- 5.2% at 100 mu g/ml and 370.2% +/- 7.2% at 400 mu g/ml) and the mitochondrial membrane depolarization (11.2% +/- 2.1% at 100 mu g/ml and 311.5% +/- 6.1% at 400 mg/ml). The SCE-induced apoptotic cell death showed the down-regulation of Bcl-2, but up-regulation of Bax. Subsequently, SCE increased the expression level of Fas/FasL, activated caspase-9 and -3, and increased reactive oxygen species generation. Also, JNK II inhibitor or a p38 MAPK inhibitor inhibited SCE-induced cell death.
Discussion and conclusion: These results indicate that SCE might be an effective chemotherapeutic for the treatment of human gastric cancer.

• 出版日期2015-2