title: Inhibition of proteasome activity in Gleditsia sinensis fruit extract-mediated apoptosis on human carcinoma cells.
abstract: The anomalous fruit extract of Gleditsia sinensis (GSE) was shown to possess anticancer potential on various solid tumour and leukaemia cell lines in vitro. We have recently demonstrated that the mitochondrial-dependent apoptotic pathway including mitochondrial membrane potential depolarization, changes in the level of reactive oxygen species and activation of caspase 3 were recruited in GSE-induced apoptosis. Whether receptor-dependent APO-1/Fas apoptotic pathway is also involved remains uncertain. Using two solid tumour cell lines, the HepG2 hepatoblastoma carcinoma cells and MDA-MB231 breast cancer cells, we demonstrated that the Fas ligand and Fas receptor protein levels did not have significant variation after GSE incubation. Caspase 8 activity increased only weakly when compared with that of caspase 3. The chrymotrypsin-like activity of proteasome was partially inhibited up to 30-40% when compared with the untreated control. Taken together, we believe that GSE- mediated apoptosis on HepG2 and MDA-MB231 carcinoma cells is mainly dictated by the mitochondrial-dependent pathway while inhibition of proteasome activity may also be involved in GSE-induced apoptosis.
authors.affiliation: State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, PR China.
authors.forename: Filly
authors.initials: F
authors.lastname: Cheung
authors.forename: Chung Hin
authors.initials: CH
authors.lastname: Chui
authors.forename: Albert Sun Chi
authors.initials: AS
authors.lastname: Chan
authors.forename: Fung Yi
authors.initials: FY
authors.lastname: Lau
authors.forename: Gregory Yin Ming
authors.initials: GY
authors.lastname: Cheng
authors.forename: Raymond Siu Ming
authors.initials: RS
authors.lastname: Wong
authors.forename: Stanton Hon Lung
authors.initials: SH
authors.lastname: Kok
authors.forename: Ivy Tuang Ngo
authors.initials: IT
authors.lastname: Teo
authors.forename: Chor Hing
authors.initials: CH
authors.lastname: Cheng
authors.forename: Johnny Cheuk On
authors.initials: JC
authors.lastname: Tang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002277:Carcinoma / Q000201:enzymology*; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D053222:Fas Ligand Protein; D005638:Fruit / Q000737:chemistry; D031501:Gleditsia / Q000737:chemistry*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D061988:Proteasome Inhibitors; D048069:Tumor Necrosis Factors / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D061988:Proteasome Inhibitors; D048069:Tumor Necrosis Factors; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases