Pseudolaric acid B-induced apoptosis through p53-dependent pathway in human gastric carcinoma cells

Abstract

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 μM and the IC₅₀ value was 0.91 μM 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.

Keywords:

• pseudolaric acid B
• p53
• Fas
• caspase-3
• bcl-2
• apoptosis

Acknowledgements

The authors gratefully thank Dr Chunyan Liu (North China Coal Medical College, China) for the excellent technical assistance and appreciate Dr Fangfang Li (Hebei Medical University, China) for her instruction in the experiments.