Antiproliferative and apoptosis-inducing activity of Brucea javanica extract on human carcinoma cells.
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.
Lau
Fung Yi
FY
State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, PR China.
Chui
Chung Hin
CH
Gambari
Roberto
R
Kok
Stanton Hon Lung
SH
Kan
Kin Luen
KL
Cheng
Gregory Yin Ming
GY
Wong
Raymond Siu Ming
RS
Teo
Ivy Tuang Ngo
IT
Cheng
Chor Hing
CH
Wan
Thomas Shek Kwong
TS
Chan
Albert Sun Chi
AS
Tang
Johnny Cheuk On
JC
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
D010936:Plant Extracts; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases