Effects And Mechanisms Of Apoptosis Induced By Bioactive Peptides Of Oyster In Peak â…  From Saccostrea Cucullata On The Human Gastric Adenocarcinoma BGC-823 Cells

In this study, we used BPO-1 (Bioactive Peptides of Oyster in Peak I ) , a group of peptides which isolated from acid extracts of Oyster (Saccostrea Cucullata), through a Sephadex G-50 column to treat the human gastric adenocarcinoma BGC-823 cells. Compared with curcumin and HMBA, we investigated the biological effects and the antitumor mechanisms of BPO-1 by the methods of cell biology, immune biology, biochemistry and molecular biology.The results revealed that the proliferation of BGC-823 cells were inhibited apparently after being treated with 4C^ig/mL BPO-1, the growth of cells were inhibited, the cell mitotic index was declined obviously, the cell cycle came into apoptosis. Biochemistry, cytochemistry and immunocytochemistry assays showed that the enzyme activity of alkaline phosphatase was declined significantly in the cells treated with 40p.g/mL BPO-1 or lO^g/mL curcumin or 30^g/mL BPO-1 combinated with 5ug/mL curcumin. Light microscopy, transmission electron microscopy showed that BGC-823 cells, which induced with BPO-1 or curcumin or their combination, had lost their original malignant phenotype which were different from those of untreated cells but were similar to those of normal apoptotic cells: the cells, including cell shrinkage, nuclear condensation, compaction and margination of nuclear chromation, and formation apoptotic bodies. Flow cytometry analysis showed BPO-1 and curcumin and their combination could induce the emergence of the peak of apoptosis. Immunocytochemistry revealed that the expression of pi6, p2rAH/UPI, c-myc, Fas were upregulated significatntly while the products of mutant p53, bcl-2 proteins were downregulated significantly in the cells treated with BPO-1 or curcumin or their combination.Taken together, the results of the current study showed that BPO-1 couldeffectively inhibit the proliferation of the human gastric adenocarcinoma BGC-823 cells, alter the activities of metabolism enzymes and the expression of antigens associated with gastric carcinoma cells, reverse the malignant morpholigical and ultrastructural characteristics, and flow cytometry analysis showed BPO-1 could induce the emergence of the phase of apoptosis. Therefore it indicated that BPO-1 has an obvious apoptosis inducing effect on the human gastric adenocarcinoma cells by regulating the expression of oncogenes and tumor suppressors genes such as mutant p53, bcl-2, c-myc, Fas, p21 WAFI/C1P1 and p16 genes.