Oleanolic acid induces apoptosis of MKN28 cells via AKT and JNK signaling pathways

Abstract

Context: 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. Materials and methods: Cell viability was assessed by MTT assay within the range of 0-160 mg/ mL. The effects of OA (5, 10 and 20 mg/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 mg/mL). Results: OA evidently inhibited cell viability with IC 50 of 44.8 and 15.9 mg/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. Conclusion: OA induces apoptosis of MKN28 cells via the mitochondrial pathway regulated by AKT and JNK signaling pathways.

Oleanolic acid induces p53-dependent apoptosis via the ERK/JNK/AKT pathway in cancer cell lines in prostatic cancer xenografts in mice

“…The expression levels of the apoptosis-associated p53, cytochrome c, Bax, caspase-3, and PARP-1 proteins significantly increased in cancer cells treated with OA. These findings were consistent with a previous report of OA-induced apoptosis in human osteosarcoma cell lines (HOS, U2-OS and MG-63), human bladder cancer (T24 cells) and human gastric cancer (MKN28) [ 17 , 31 – 32 ].…”

Tanshinone IIA inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cells via p53‑cyclin B1/CDC2

“…In summary, a combined application of surgery, radiotherapy and chemotherapy demonstrates an improved treatment effect; however, these treatments may cause different degrees of throat injury, hyperemia and edema (21). Considering the present treatment options, there is as requirement to investigate Chinese medicines that may be administered to patients following surgery, radiotherapy and chemotherapy to reduce postoperative recurrence and metastasis, decrease the side effects of chemotherapy, and improve the quality of life and the survival rate (22). The present results demonstrated that tanshinone IIA could inhibit cell proliferation and induce apoptosis of human nasopharyngeal carcinoma cells.…”

Ethanol Extract of Oldenlandia diffusa – an Effective Chemotherapeutic for the Treatment of Colorectal Cancer in Humans

“…OA was also reported to induce the apoptosis of MKN28 cells (a gastric cancer cell line) via the mitochondrial pathway in an AKT and c-Jun N-terminal kinase (JNK) dependent manner, and interestingly, OA increased JNK phosphorylation, and decreased AKT phosphorylation, but did not affect the phosphorylations of p38 and extracellular signal-regulated kinase (ERK). Furthermore, OA also enhanced the messenger RNA (mRNA) expressions of caspase 3, caspase 9 and Apaf-1 in MKN28 cells significantly [ 18 ]. In HepG2 cells (a hepatocellular carcinoma cell-line), OA inhibited hepatocellular carcinoma via ERK-p53 induced cell cycle arrest and mitochondrial-dependent apoptosis [ 19 ].…”