Pseudolaric acid B-induced apoptosis through p53-dependent pathway in human gastric carcinoma cells.
Pseudolaric acid B (PLAB, 1), a natural diterpenoid compound, was isolated from Pseudolarix kaempferi Gordon. It has shown antifungal, antifertility, and antiangiogenic properties in previous studies. Recently, increasing evidence has confirmed that 1 exhibits antitumor effects in several tumor cell lines, but the underlying mechanism has not been fully elucidated. The aim of this study was to investigate the mechanism of PLAB-induced cell apoptosis in MGC803 cells. The results showed that 1 significantly inhibited the proliferation of MGC803 cells at 0.01-10 microM and the IC(50) value was 0.91 microM for 48 h. PLAB-induced apoptosis in MGC803 cells was confirmed by DNA fragmentation assay and Hoechst33342/PI staining. PLAB-treated MGC803 cells were arrested at G(2) phase, which was associated with a marked increment of the expression of cyclin-dependent kinase inhibitor p21. The induction of p21 appeared to be transcriptionally up-regulated and was p53-dependent. In addition, PLAB induced Fas/APO-1 and caspase-3 expressions that were also correlated with apoptosis. Meanwhile, 1 decreased the mRNA expression of bcl-2, which is an antiapoptosis factor. In conclusion, 1 induced apoptosis through p53-dependent pathway in human gastric carcinoma cells. These findings suggest that 1 may be a novel promising agent for treating human gastric carcinoma.
Meng
Ai-Guo
AG
Department of Biochemistry, Hebei Medical University, Shijiazhuang, China.
Jiang
Ling-Ling
LL
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D028201:Pinaceae / Q000737:chemistry; D013274:Stomach Neoplasms / Q000188:drug therapy*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D019014:fas Receptor / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; C058391:pseudolaric acid B; D053148:Caspase 3