title: Beta-eleostearic acid induce apoptosis in T24 human bladder cancer cells through reactive oxygen species (ROS)-mediated pathway.
abstract: Beta-eleostearic acid (β-ESA, 9E11E13E-18:3), a linolenic acid isomer with a conjugated triene system, is a natural and biologically active compound. Herein, we investigated effects of β-eleostearic acid on T24 human bladder cancer cells. In this study, results showed that β-eleostearic acid had strong cytotoxicity to induce cell apoptosis, which was mediated by reactive oxygen species (ROS) in T24 cells. The cell viability assay results showed that incubation with β-eleostearic acid concentrations of 10-80μmol/L caused a dose- and time-dependent decrease of T24 cell viability, and the IC(50) value was 21.2μmol/L at 24h and 13.1μmol/L at 48h. Annexin V/PI double staining was used to assess apoptosis with flow cytometry. Treatment with β-eleostearic acid caused massive ROS accumulation and GSH decrease, which lead to activation of caspase-3 and down-regulation of Bcl-2 indicating induction of apoptosis. Subsequently, N-acetyl-l-cysteine (NAC) and PEG-catalase effectively blocked the ROS elevated effect of β-eleostearic acid, which suggested that β-eleostearic acid-induced apoptosis involved ROS generated. Additionally, we found that treating T24 cells with β-eleostearic acid induced activation of PPARγ. A PPARγ-activated protein kinase inhibitor was able to partially abrogate the effects of β-eleostearic acid. These results suggested that β-eleostearic acid can induce T24 cells apoptosis via a ROS-mediated pathway which may be involved PPARγ activation.
authors.affiliation: Liaoning Key Laboratory of Food Biological Technology, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Sun
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.forename: Shuhong
authors.initials: S
authors.lastname: Ye
authors.forename: Shan
authors.initials: S
authors.lastname: Xiao
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Jiang
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Jihui
authors.initials: J
authors.lastname: Wang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008042:Linolenic Acids / Q000494:pharmacology*; D047495:PPAR gamma / Q000037:antagonists & inhibitors; D011092:Polyethylene Glycols / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism
chemical_list: D000975:Antioxidants; D061945:Caspase Inhibitors; D008042:Linolenic Acids; D047495:PPAR gamma; D017382:Reactive Oxygen Species; C070295:catalase-polyethylene glycol; C004934:eleostearic acid; D011092:Polyethylene Glycols; D002374:Catalase; D053148:Caspase 3; D005978:Glutathione; D000111:Acetylcysteine