Orostachys japonicus induces apoptosis and cell cycle arrest through the mitochondria-dependent apoptotic pathway in AGS human gastric cancer cells.
We investigated the anticancer mechanisms of the ethylacetate (EtOAc) fraction from Orostachys japonicus in human gastric cancer (AGS) cells. Flow cytometric analysis revealed that the number of total apoptotic cells following treatment with the EtOAc fraction increased in a dose-dependent manner. In the cell cycle analyses, the EtOAc fraction increased the peak in the sub-G1, indicating apoptosis, and in the G₂/M phases in a dose-dependent manner. In the RT-PCR analysis, the expression of cyclin-dependent kinase 1 (CDK 1) and cyclin B1 decreased in a dose- and time-dependent manner. The results of western blotting revealed that the protein levels of p53, cytochrome c, and cleaved caspase-3, -8 and -9 proteins increased and those of B cell lymphoma-2 (bcl-2) and pro-caspase-3, -8 and -9 proteins decreased in a dose- and time-dependent manner, whereas the levels of bcl-2-associated x protein (bax) remained unchanged. Furthermore, the changes in the levels of pro-caspase-3, -8 and -9 and cleaved caspase-3, -8 and -9 were abolished by the pan-caspase inhibitor Z-VAD-FMK. In addition, phosphorylation of p38 and JNK increased in a time-dependent manner. These results, for the first time, provide an understanding of the potential anticancer activity of the O. japonicus, which functions through the induction of apoptosis and cell cycle arrest.
Department of Biomedical Laboratory Science, Inje University, Gimhae, Gyungnam 621-749, Republic of Korea.
Deok-Seon
DS
Ryu
Department of Smart Foods and Drugs, Graduate School of Inje University, Gimhae, Gyungnam 621-749, Republic of Korea.
Seon-Hee
SH
Kim
Department of Smart Foods and Drugs, Graduate School of Inje University, Gimhae, Gyungnam 621-749, Republic of Korea.
Ji-Hae
JH
Kwon
Department of Biomedical Laboratory Science, Inje University, Gimhae, Gyungnam 621-749, Republic of Korea.
Dong-Seok
DS
Lee
D000085:Acetates / Q000008:administration & dosage* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D029627:Crassulaceae / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D010766:Phosphorylation; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000473:pathology*
D000085:Acetates; D000970:Antineoplastic Agents; D010936:Plant Extracts; C007650:ethyl acetate