ATM-p53 pathway causes G2/M arrest, but represses apoptosis in pseudolaric acid B-treated HeLa cells

作者:Yao, Guodong; Qi, Min; Ji, Xiaoling; Fan, Simiao; Xu, Lei; Hayashi, Toshihiko; Tashiro, Shin-ichi; Onodera, Satoshi; Ikejima, Takashi*
来源:Archives of Biochemistry and Biophysics, 2014, 558: 51-60.
DOI:10.1016/j.abb.2014.05.029

摘要

Pseudolaric acid B (PAB) is a diterpene acid, isolated from the root and trunk bark of Pseudolarix kaempferi Gordon (Pinaceae). Previous studies demonstrated that PAB induced G2/M arrest and apoptosis in several cancer cell lines, but the relationship between G2/M arrest and apoptosis is still unclear. We examined the relevant signaling pathways for human cervical carcinoma HeLa cells treated with 1 mu M PAB. Intriguingly, we found that activation of ATM-p53 signaling pathway by the treatment with 1 mu M PAB played a protective role for the subsequent apoptosis. Although the treatment with 1 mu M PAB up-regulated the expression of cyclin B1 and p-Histone 3 (mitotic markers) at 12 h, the expression decreased at 24 and 36 h along with the up-down expression of mitotic markers. The expressions of p-ATM and p-p53 that were involved in G2/M arrest increased at 12 h after treatment with PAB. However, a prolonged treatment with PAB (longer than 24 h) caused cell apoptosis. When the cells were arrested in G1 or S phase by the treatment with serum starvation, cytosine beta-D-arabinofuranoside (Ara-C) or hydroxyurea (Hu), the apoptotic ratio induced by PAB decreased.