Effects and mechanism of natural product gochnatiolide A on proliferation and apoptosis of human prostate cancer DU145 cells / 中草药

ABSTRACT

Objective: To investigate the effects and mechanism of gochnatiolide A from Ainsliaea in anti-prostate cancer. Methods: The activities of gochnatiolide A on the proliferation of DU145 cells were tested by CCK-8 and colony formation experiments. Apoptosis morphological changes of cells were observed by DAPI staining. The apoptosis and cell cycle were evaluated by flow cytometry. The expressions of cleaved Poly ADP ribose polymerase (cleaved-PARP), cleaved cystein-containing aspartate specific protease 9 (cleaved Caspase-9), tumor suppressor protein (p53), b cell lymphoma-2 (Bcl-2), transcription factors-κB p65 (NF-κB p65) and IκB kinase α, β (IKKα, IKKβ) proteins in DU145 cells were investigated by Western blotting. Results: The natural product gochnatiolide A significantly inhibited the proliferation of prostate cancer DU145 cells, with IC50 values of 4.15, 2.80 and 1.74 μmol/L at 12 h, 24 h, and 48 h, respectively. Meanwhile, gochnatiolide A promoted DU145 cells apoptosis and induced cell cycle arrest at G2 and S phases in a concentration dependent manner. In addition, gochnatiolide A also up-regulated apoptosis proteins cleaved-PARP, cleaved Caspase-9 and p53 proteins, and down-regulated Bcl-2 protein. Comparing the control group, the expression of NF-κB p65, IKKα and IKKβ proteins in the NF-κB pathway were decreased after treatment with gochnatiolide A. Conclusion: The natural product gochnatiolide A remarkably inhibited the proliferation and promoted apoptosis in DU145 cells, and the possible mechanism was related to the inhibition of NF-κB pathway.