Oleanolic acid induces apoptosis of MKN28 cells via AKT and JNK signaling pathways.
BACKGROUND
Oleanolic acid (OA) belongs to the triterpenoid compound group existing widely in food, medicinal herbs and other plants. Its effects on gastric cancer cells and the mechanisms involved have not been investigated.


OBJECTIVE
This study aimed to substantiate whether OA induces apoptosis of gastric cancer cell line (MKN28) and to elucidate the molecular mechanism involved.


METHODS
Cell viability was assessed by MTT assay within the range of 0-160 μg/mL. The effects of OA (5, 10 and 20 μg/mL) on apoptosis of MKN28 cells were evaluated by flow cytometry, DNA fragmentation and mitochondrial membrane potential assays. Western blot and FQRT-PCR assays were used to investigate the mechanism of cell apoptosis induced by OA (5 and 10 μg/mL).


RESULTS
OA evidently inhibited cell viability with IC50 of 44.8 and 15.9 μg/mL at 12 and 24 h, respectively. Furthermore, OA increased JNK phosphorylation, decreased AKT phosphorylation, but did not affect p38 and ERK phosphorylation in MKN28 cells. In contrast, OA also significantly enhanced the mRNA expression levels of caspase 3, caspase 9 and Apaf-1 in MKN28 cells.


CONCLUSIONS
OA induces apoptosis of MKN28 cells via the mitochondrial pathway regulated by AKT and JNK signaling pathways.
Department of Gastroenterology, Sixth People's Hospital, Shanghai Jiao Tong University , Shanghai , China.
Yunmin
Y
Lu
Meiying
M
Zhu
Wei
W
Chen
Li
L
Yin
Jinshui
J
Zhu
Niwei
N
Chen
Weixiong
W
Chen
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009828:Oleanolic Acid / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D009828:Oleanolic Acid; D051057:Proto-Oncogene Proteins c-akt
Gastric cancer; mitochondria; natural product