Inhibition of proteasome activity in Gleditsia sinensis fruit extract-mediated apoptosis on human carcinoma cells.
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.
Cheung
Filly
F
State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, PR China.
Chui
Chung Hin
CH
Chan
Albert Sun Chi
AS
Lau
Fung Yi
FY
Cheng
Gregory Yin Ming
GY
Wong
Raymond Siu Ming
RS
Kok
Stanton Hon Lung
SH
Teo
Ivy Tuang Ngo
IT
Cheng
Chor Hing
CH
Tang
Johnny Cheuk On
JC
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
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