Luteolin induces apoptosis in vitro through suppressing the MAPK and PI3K signaling pathways in gastric cancer

Abstract

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.

Luteolin Suppresses the Proliferation of Gastric Cancer Cells and Acts in Synergy with Oxaliplatin

“…LUT exerts cytoprotective effects against lipid peroxidation products and led to apoptosis of PC12 cells by inducing the phosphorylation of ERK1/2, JNK, and P38 MAPK signal transduction [27]. Moreover, it induced apoptosis by inhibiting PI3K/AKT and ERK1/2 MAPK intracellular signaling and increasing the levels of apoptotic proteins in gastric cancer BGC 823 cells [28]. Moreover, LUT was shown to function as an enhancer, sensitizing cells to doxorubicin-induced autophagy signaling in human osteosarcoma cells [29].…”

Stevia Eupatoria and Stevia Pilosa Extracts Inhibit the Proliferation and Migration of Prostate Cancer Cells

“…Stevia pilosa and Stevia eupatoria extracts have compounds such as luteolin, quercetin, β-sitosterol, stigmasterol [11], seco-triterpenes [17], and longipinenes [18]. Luteolin has shown cellular arrest and apoptosis induction in many types of cancer cell lines, such as prostate cancer (PC-3), liver cancer (SMMC7721), colon cancer (COLO205), and cervical cancer (HeLa) [19]. Quercetin decreases the viability and proliferation of MCF-7 breast cancer cells through apoptosis activation, via increasing the levels of Bcl-2-associated X protein (BAX) and caspase-3 expression and decreasing Bcl-2 expression.…”

Analysis of plasma migration components in Patrinia villosa (Thunb.) Juss. effective parts by UPLC–Q‐TOF–MS

“…The Consulting the literature showed that the phenolic acid components chlorogenic acid (Xue et al, 2017;Shao, Zhang, Chen, & Sun, 2015) and caffeic acid (Brautigan, Gielata, Heo, Kubicka, & Wilkins, 2018), and the flavonoids scutellarin (Nie et al, 2018;Sun et al, 2018;Tang & Gao, 2019), isoorientin (Huang, Jin et al, 2018;Lin et al, 2016), isovitexin (Lv, 2018), scutellarein (Jiang et al, 2018;Lu, Li, Li, & Asia, 2017;Zheng et al, 2017), luteolin (Niu, Guo, Gan, Bao, & Ren, 2015) and apigenin (Bhattacharya et al, 2018;Masuelli et al, 2017;Cai et al, 2011) had different degrees of inhibition on tumor cells. Among them, caffeic acid, isoorientin, isovitexin, luteolin and apigenin had better antiliver tumor activities.…”