Title:Eriocalyxin B-Induced Apoptosis in Pancreatic Adenocarcinoma Cells Through Thiol-Containing Antioxidant Systems and Downstream Signalling Pathways
Volume: 14
Issue: 5
Author(s): L. Li, G.G.L. Yue, J.X. Pu, H.D. Sun, K.P. Fung, P.C. Leung, Q.B. Han, C.B.S. Lau and P.S. Leung
Affiliation:
Keywords:
Apoptosis, eriocalyxin B, pancreatic cancer, reactive oxygen species, thiols.
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.
