Xu, JC (reprint author), Chinese Acad Sci, Kunming Inst Bot, Key Lab Plant Biodivers & Biogeog East Asia, Kunming 650201, Yunnan, Peoples R China.
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, NF kappa B 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.
1.Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China 2.Chinese Univ Hong Kong, Inst Chinese Med, Hong Kong, Peoples R China 3.Chinese Univ Hong Kong, State Key Lab Phytochem & Plant Resources West Ch, Hong Kong, Peoples R China 4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Mengla, Yunnan, Peoples R China 5.Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China
Li,L.;Yue,G.G. L.;Pu,J.X.;Sun,H.D.;Fung,K.P.;Leung,P.C.;Han,Q.B.;Lau,C.B.S.;Leung,P.S..Eriocalyxin B-Induced Apoptosis in Pancreatic Adenocarcinoma Cells Through Thiol-Containing Antioxidant Systems and Downstream Signalling Pathways,CURRENT MOLECULAR MEDICINE,2014,14(5):673-689