title: Antiproliferative and apoptosis-inducing activity of Brucea javanica extract on human carcinoma cells.
abstract: We have recently demonstrated the antiproliferative and apoptotic activities of herbal traditional Chinese medicines, including the analomous fruit extract of Gleditsia sinensis, the fresh juice of Scutellaria barbata and the warmed water extract of Radix Sophorae Tonkinensis on a series of human carcinoma cells. Here, we further report the potential anti-cancer activity of the warmed water extract of Brucea javanica (BJE). Four cancer cell lines, including A549 non-small cell lung cancer, Hep3B hepatocellular carcinoma, MDA-MB231 breast cancer and SLMT-1 oesophageal squamous cell carcinoma, were incubated with BJE and strong apoptotic induction was observed under inverted microscopic investigation for all of the four cell lines tested. Using the MDA-MB231 breast cancer cell line as an experimental model, additional analyses supported the hypothesis that the mitochondrial membrane potential depolarization pathway was induced by BJE. The APO-1/Fas receptor death induction pathway was not activated under the influence of BJE, as studied by staining with Fas ligand and Fas receptor specific antibodies. Accordingly, only weak activation of caspase 8 was observed upon BJE treatment. On the other hand, caspase 3 activity was stimulated up to five-fold in BJE-treated cells compared to untreated controls. Oligonucleosomal DNA fragmentation formation was detected by labelling the nucleic acid ladders with TdT-mediated dUTP nick end labelling. Collectively, BJE-induced cancer cell death proceeds through a mitochondrial dependent pathway associated with caspase 3 activation.
authors.affiliation: State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, PR China.
authors.forename: Fung Yi
authors.initials: FY
authors.lastname: Lau
authors.forename: Chung Hin
authors.initials: CH
authors.lastname: Chui
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Stanton Hon Lung
authors.initials: SH
authors.lastname: Kok
authors.forename: Kin Luen
authors.initials: KL
authors.lastname: Kan
authors.forename: Gregory Yin Ming
authors.initials: GY
authors.lastname: Cheng
authors.forename: Raymond Siu Ming
authors.initials: RS
authors.lastname: Wong
authors.forename: Ivy Tuang Ngo
authors.initials: IT
authors.lastname: Teo
authors.forename: Chor Hing
authors.initials: CH
authors.lastname: Cheng
authors.forename: Thomas Shek Kwong
authors.initials: TS
authors.lastname: Wan
authors.forename: Albert Sun Chi
authors.initials: AS
authors.lastname: Chan
authors.forename: Johnny Cheuk On
authors.initials: JC
authors.lastname: Tang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects; D032269:Brucea / Q000737:chemistry*; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D019014:fas Receptor / Q000378:metabolism
chemical_list: D010936:Plant Extracts; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases