Abstract
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 1μM PAB. Intriguingly, we found that activation of ATM–p53 signaling pathway by the treatment with 1μM PAB played a protective role for the subsequent apoptosis. Although the treatment with 1μM PAB up-regulated the expression of cyclin B1 and p-Histone 3 (mitotic markers) at 12h, the expression decreased at 24 and 36h 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 12h after treatment with PAB. However, a prolonged treatment with PAB (longer than 24h) caused cell apoptosis. When the cells were arrested in G1 or S phase by the treatment with serum starvation, cytosine β-d-arabinofuranoside (Ara-C) or hydroxyurea (Hu), the apoptotic ratio induced by PAB decreased.
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