Mechanisms of (2-methyl-n-butyl) shikonin induced apoptosis of gastric cancer SGC-7901 cells.
- Author:
Hai-Bing WANG
1
;
Xiao-Qiong MA
Author Information
1. National Clinical Research Base of Traditional Chinese Medicine, the First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310006, China.
- Publication Type:Journal Article
- MeSH:
Antineoplastic Agents, Phytogenic;
chemistry;
isolation & purification;
pharmacology;
Apoptosis;
drug effects;
Caspase 3;
metabolism;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Dose-Response Relationship, Drug;
Drugs, Chinese Herbal;
chemistry;
isolation & purification;
pharmacology;
Humans;
Inhibitory Concentration 50;
Lithospermum;
chemistry;
MAP Kinase Signaling System;
drug effects;
Membrane Potential, Mitochondrial;
drug effects;
Molecular Structure;
Naphthoquinones;
chemistry;
isolation & purification;
pharmacology;
Plant Roots;
chemistry;
Plants, Medicinal;
chemistry;
Proto-Oncogene Proteins c-bcl-2;
metabolism;
Stomach Neoplasms;
metabolism;
pathology
- From:
Acta Pharmaceutica Sinica
2012;47(6):816-821
- CountryChina
- Language:Chinese
-
Abstract:
This study is to investigate the effect of (2-methyl-n-butyl) shikonin (MBS) on inducing apoptosis of human gastric cancer cell line SGC-7901 and the role of ERK1/2 signal pathway in the apoptosis. MTT assay was used to detect SGC-7901 cell proliferation. DNA condensation was measured by DAPI stain. Cell apoptosis was analyzed by flow cytometry. Mitochondrial membrane potential (MMP) was analyzed by JC-1 staining. The protein expressions of Bcl-2, Bax, Survivin, cleaved caspase-9, cleaved caspase-3, cleaved PARP, p-ERK1/2, ERK1/2, p-JNK, JNK, p-p38 and p38 were detected by Western blotting. The results showed that MBS reduced the cell viability of SGC-7901 cells in a dose- and time-dependent manner. The IC50 at 24 h and 48 h for SGC-7901 cells was 10.113 and 4.196 micromolL(-1), respectively. After being treated with MBS, the typical nuclear condensation was observed in SGC-7901 cells by DAPI stain. Apoptosis in SGC-7901 cells was induced by MBS in a dose dependent manner. The protein expression of Bcl-2 was down-regulated, while the protein expressions of cleaved caspase-9, cleaved caspase-3, cleaved PARP, p-ERK1/2 and p-JNK were up-regulated after MBS treatment. U0126, a specific MAP kinase (MEK1/2) inhibitor, blocked the ERK1/2 activation by MBS. MMP was decreased by MBS treatment. It can be concluded that MBS could inhibit SGC-7901 cell proliferation and induce apoptosis. Mitochondrial apoptosis pathway, ERK1/2 signal pathway and JNK signal pathway might be involved in this process.
