title: Eriocalyxin B-induced apoptosis in pancreatic adenocarcinoma cells through thiol-containing antioxidant systems and downstream signalling pathways.
abstract: Thiol-containing antioxidant systems play an important role in regulating cellular redox homeostasis. Several anti-cancer agents act by targeting these systems by inducing the production of reactive oxygen species (ROS). Our earlier studies have shown that Eriocalyxin B (EriB), a diterpenoid isolated from Isodon eriocalyx, possesses anti-pancreatic tumour activities in vitro and in vivo. The present study further demonstrated that only thiol-containing antioxidants, N-acetylcysteine (NAC) or dithiothreitol (DTT), inhibited EriB-induced cytotoxicity and apoptosis. EriB suppressed the glutathione and thioredoxin antioxidant systems, thus increasing the intracellular ROS levels and regulating the MAPK, NFκB pathways. Treatment with EriB depleted the intracellular thiol-containing proteins in CAPAN-2 cells. In vivo studies also showed that EriB treatment (2.5 mg/kg) reduced the pancreatic tumour weights significantly in nude mice with increased superoxide levels. Taken together, our results shed important new light on the molecular mechanisms of EriB acting as an apoptogenic agent and its therapeutic potential for pancreatic cancer.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: G G L
authors.initials: GG
authors.lastname: Yue
authors.forename: J X
authors.initials: JX
authors.lastname: Pu
authors.forename: H D
authors.initials: HD
authors.lastname: Sun
authors.forename: K P
authors.initials: KP
authors.lastname: Fung
authors.forename: P C
authors.initials: PC
authors.lastname: Leung
authors.forename: Q B
authors.initials: QB
authors.lastname: Han
authors.forename: C B S
authors.initials: CB
authors.lastname: Lau
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shain, New Territories Hong Kong, China. psleung@cuhk.edu.hk.
authors.forename: P S
authors.initials: PS
authors.lastname: Leung
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D004224:Diterpenes; D017382:Reactive Oxygen Species; C516552:eriocalyxin B; D005978:Glutathione