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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 5; p. 1073
• Main Authors: Ryu, Mina, Sung, Chung Ki, Im, Young Jun, Chun, ChangJu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 27.02.2020; MDPI AG
• Subjects: Alnus - chemistry; alnus hirsuta; Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; cell cycle; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Survival - drug effects; diarylheptanoid; Diarylheptanoids - pharmacology; Humans; Inhibitory Concentration 50; jnk; JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Signaling System - drug effects; mapk; mcf-7 cells; p38; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Reactive Oxygen Species - metabolism; ros; Saccharomyces cerevisiae - drug effects; Alnus hirsuta; p38; cell cycle; JNK; ROS; MCF-7 cells; apoptosis; MAPK; diarylheptanoid
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25051073

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.