[Mechanisms of (2-methyl-n-butyl) shikonin induced apoptosis of gastric cancer SGC-7901 cells].
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.
National Clinical Research Base of Traditional Chinese Medicine, the First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou 310006, China.
Hai-Bing
HB
Wang
Xiao-Qiong
XQ
Ma
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D029684:Lithospermum / Q000737:chemistry*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*
C583586:(2-methyl-n-butyl)shikonin; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3