Induction of apoptosis in SGC-7901 cells by polysaccharide-peptide GFPS1b from the cultured mycelia of Grifola frondosa GF9801

• Published in: Toxicology in vitro 2007-04, Vol.21 (3), p.417-427
• Main Authors: Cui, Feng-Jie, Li, Yin, Xu, Ying-Ying, Liu, Zhi-Qiang, Huang, Da-Ming, Zhang, Zhi-Cai, Tao, Wen-Yi
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Bax; Bcl-2; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Caspase-3; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; DNA Damage; Drug Screening Assays, Antitumor; Gene Expression Regulation, Neoplastic - drug effects; Grifola - chemistry; Grifola - metabolism; Grifola frondosa; Hepatocytes - drug effects; Hepatocytes - ultrastructure; Humans; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondria - ultrastructure; Mitochondrial membrane potential; Mycelium - chemistry; Plant Extracts - pharmacology; Polysaccharide-peptide; Polysaccharides - pharmacology; Proteoglycans - pharmacology; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2006.10.004

The biological function of GFPPS1b, a novel polysaccharide-peptide isolated from cultured mycelia of Grifola frondosa GF9801, was well investigated. GFPS1b has anti-tumor activity and can significantly inhibit the proliferation of SGC-7901 cells, whereas slightly influences the growth of human normal liver cell line L-02. When treated with GFPS1b, SGC-7901 cells showed typical apoptotic morphological features such as the loss of villus and appearance of apoptotic bodies on the cell surface, volume reduction, and chromatin condensation, by scanning electron microscopy (SEM) and fluorescent microscopy (Hoechst 33342). The results of flow cytometry analysis and annexin V-PI assay showed that the SGC-7901 cell cycle was arrested in the G 2/M phase, the subdiploid peak of DNA characteristic of apoptotic was also observed, and the apoptosis ratio was about 15.08%. DNA isolated from SGC-7901 cells cultured with GFPS1b showed a typical DNA ‘ladders’ of apoptosis in agarose gel electrophoresis. Further investigation results showed that the apoptotic machinery of SGC-7901 induced by GFPS1b was associated with drop in mitochondrial trans-membrane potential, upregulation of Bax, downregulation of Bcl-2, and activation of caspase-3. Our finding suggests that GFPS1b could suppress SGC-7901 cell growth and reduce cell survival via arresting cell cycle and inducing apoptosis of tumor cells.