@article{APS9382,
author = {Guo-dong Yao and Jing Yang and Qiang Li and Ye Zhang and Min Qi and Si-miao Fan and Toshihiko Hayashi and Shin-ichi Tashiro and Satoshi Onodera and Takashi Ikejima},
title = {Activation of p53 contributes to pseudolaric acid B-induced senescence in human lung cancer cells in vitro},
journal = {Acta Pharmacologica Sinica},
volume = {37},
number = {7},
year = {2017},
keywords = {},
abstract = {Aim: Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi Gordon, has shown to exert anti-tumor effects via inducing cell cycle arrest followed by apoptosis in several cancer cell lines. Here we reported that PAB induced a mitotic catastrophe in human lung cancer A549 cells, which resulted in senescence without apoptosis or necrosis.
Methods: Three human lung cancer cell lines (A549, H460 and H1299 cells) were examined. Cell growth inhibition was assessed with MTT assay. Cell cycle distribution was determined using a flow cytometer. Cell nuclear morphology was observed under a fluorescence microscope. Senescent cells were detected using SA-β-Gal staining. Apoptotic and senescent protein expression was examined using Western blot analysis. The expression of p53 and p21 in the cells was downregulated by siRNAs.
Results: Treatment with PAB (5–80 μmol/L) inhibited the growth of A549 cells in dose- and time-dependent manners. Prolonged treatment with PAB (20 μmol/L) caused G2/M arrest at day 1 followed by mitotic catastrophe from day 2, which eventually resulted in cell senescence between days 3 and 4 without cell death (apoptosis or necrosis). Knockdown of p53 expression with siRNA significantly suppressed PAB-induced senescence in A549 cells (p53 wild). Furthermore, PAB-induced senescence was also observed in human lung cancer H460 cells (p53 wild), but not in human lung cancer H1299 cells (p53 null).
Conclusion: The anti-tumor action of PAB against human lung cancer A549 cells in vitro involves the induction of senescence through activation of the p53 pathway.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9382}
}