TY - JOUR AB - Luteolin, an active component of traditional Chinese medicine, exhibits potential for anti-tumor proliferation; however, the molecular events occurring in such process and the signal transduction pathways involved are currently unknown. Our group previously reported that luteolin inhibited proliferation and induced apoptosis in the gastric cancer cell line BGC-823. The aim of the present study was to investigate the mechanism by which the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling pathways regulate the apoptosis in vitro of BGC-823 cells following treatment with luteolin. It was observed that luteolin induced apoptosis through the intrinsic pathway by increasing the levels of caspase-3, caspase-9 and cytochrome c, and the ratio of B-cell lymphoma (Bcl)-2 associated X protein (Bax) to Bcl-2. Luteolin suppressed the phosphorylation of extracellular signal-regulated kinase in the MAPK signaling pathway, as well as suppressing the phosphorylation of AKT, PI3K and mechanistic target of rapamycin in the PI3K signaling pathway. In addition, luteolin combined with LY294002 markedly increased the Bax/Bcl-2 ratio, while when combined with U0126, luteolin had less effects on the Bax/Bcl-2 ratio compared with luteolin treatment alone, suggesting that both the MAPK and PI3K signaling pathways are involved in the apoptosis induced by luteolin. Furthermore, luteolin attenuated the MAPK and PI3K signaling pathways by increasing the expression of specific dual-specificity phosphatases and decreasing the expression of chemokine (C-X-C motif) ligand 16 at the messenger RNA level, respectively. Taken together, the present results demonstrate that luteolin is a potential chemotherapeutic agent against gastric cancer by exerting a dual inhibition on the MAPK and PI3K signaling pathways. AD - The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, Xinjiang 830011, P.R. China Xinjiang Key Laboratory of Special Species Conservation and Regulatory Biology, College of Life Science, Xinjiang Normal University, Urumqi, Xinjiang 830054, P.R. China AU - Lu,Xueying AU - Li,Yanhong AU - Li,Xiaobo AU - Aisa,Haji ,Akber DA - 2017/08/01 DO - 10.3892/ol.2017.6380 EP - 2000 IS - 2 JO - Oncol Lett KW - luteolin gastric carcinoma MAPK PI3K DUSPs CXCL16 PY - 2017 SN - 1792-1074 1792-1082 SP - 1993 ST - Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer T2 - Oncology Letters TI - Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer UR - https://doi.org/10.3892/ol.2017.6380 VL - 14 ER -