ABSTRACT
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. Alnus hirsuta, which contains abundant diarylheptanoids derivatives, is a valuable medicinal plant. The CHCl3 extract (AHC) containing platyphyllenone (1) and platyphyllone (3) as main compounds showed in vitro anticancer effects. We report the biological activities of A. hirsuta 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 1 and 3 and the AHC extract exhibited cytotoxic effects on MCF-7 cells in MTT assay, with IC50 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 A. hirsuta extract is achieved by apoptosis promotion and cell cycle arrest mediated by the activation of JNK and p38 signaling pathway via ROS generation.
Subject(s)
Alnus/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Diarylheptanoids/pharmacology , JNK Mitogen-Activated Protein Kinases/metabolism , Plant Extracts/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Humans , Inhibitory Concentration 50 , MAP Kinase Signaling System/drug effects , Phosphorylation/drug effects , Plant Extracts/isolation & purification , Reactive Oxygen Species/metabolism , Saccharomyces cerevisiae/drug effectsABSTRACT
BACKGROUND: LipoKinetix (Syntrax, Cape Girardeau, Missouri) is a dietary supplement marketed for weight loss. OBJECTIVE: To describe a possible causal association between LipoKinetix and hepatotoxicity. DESIGN: Case series. SETTING: Outpatient clinic, tertiary care hospital, and U.S. Food and Drug Administration databases. INTERVENTION: Routine medical and supportive care. MEASUREMENTS: Clinical and laboratory evaluation. RESULTS: All patients developed acute hepatotoxicity within 3 months of starting LipoKinetix. At presentation, symptoms and results of laboratory tests were characteristic of acute hepatitis. All patients recovered spontaneously after LipoKinetix use was discontinued. Three of the seven patients, including one who developed fulminant hepatic failure complicated by cerebral edema, were taking LipoKinetix alone at the time of presentation. Of the four patients who were taking multiple supplements, two resumed taking supplements other than LipoKinetix without incident. CONCLUSIONS: The use of LipoKinetix may be associated with hepatotoxicity. Despite extensive evaluations, no other cause for hepatotoxicity could be identified in the seven patients studied.
