Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Extract.

JNK and p38 are important mitogen-activated protein kinases (MAPKs) that respond to stress stimuli. The stress-activated MAPKs associated with apoptotic cell death play vital roles in mammalian cells. , which contains abundant diarylheptanoids derivatives, is a valuable medicinal plant. The CHCl extract (AHC) containing platyphyllenone () and platyphyllone () as main compounds showed in vitro anticancer effects. We report the biological activities of extract associated with the regulation of apoptosis and JNK and p38 in MCF-7 breast cancer cells. Levels of phospho-JNK and phospho-p38 by AHC treatment were evaluated by enzyme-linked immunosorbent assay (ELISA). ROS production, apoptotic effect, and DNA contents of the cells were measured by flow cytometry. The two diarylheptanoids and and the AHC extract exhibited cytotoxic effects on MCF-7 cells in MTT assay, with IC values of 18.1, 46.9, 260.0 μg/mL, respectively. AHC induced ROS generation and elevated the endogenous levels of phospho-JNK and phospho-p38. AHC resulted in apoptosis and cell cycle arrest. We suggest that the antitumor effect of extract is achieved by apoptosis promotion and cell cycle arrest mediated by the activation of JNK and p38 signaling pathway via ROS generation.