<p>Zeaxanthin Induces Apoptosis via ROS-Regulated MAPK and AKT Signaling Pathway in Human Gastric Cancer Cells</p>

Abstract

Background Zeaxanthin, a carotenoid commonly found in plants, has a variety of biological functions including anti-cancer activity. Purpose This study aimed to investigate the potential mechanisms of zeaxanthin in human gastric cancer cells. Methods CCK-8 assay was used to examine the cytotoxic effect of zeaxanthin on human gastric cancer cells. Flow cytometry was used to analyse AGS cell cycle distribution and apoptosis status. Western blot analysis was used to detect the expression levels of cycle-related proteins (Cyclin A, Cyclin B1, CDK1/2, p21, and p27), apoptosis-related proteins (Bcl-2, Bad, caspase-3, PARP), MAPK, AKT, STAT3, and NF-κB. Results CCK-8 assay showed that zeaxanthin has obvious cytotoxic effects on 12 types of human gastric cancer cells, but no obvious toxic effect on normal cells. In addition, flow cytometry and Western blotting results showed that zeaxanthin induces apoptosis by reducing mitochondrial membrane potential; increasing Cytochrome C, Bax, cleaved-caspase-3 (cle-cas-3), and cleaved-PARP (cle-PARP) expression levels; and decreasing Bcl-2, pro-caspase-3 (pro-cas-3), and pro-PARP expression levels. Additionally, zeaxanthin caused cell cycle arrest at the G2/M phase by increasing the levels of p21 and p27 and reduced the levels of AKT, Cyclin A, Cyclin B1, and Cyclin-dependent kinase 1/2 (CDK1/2). Furthermore, after zeaxanthin treatment, the expression levels of reactive oxygen species (ROS), p-JNK, p-p38, and I-κB increased, and the expression levels of p-ERK, p-AKT, STAT3, and NF-κB decreased. However, the ROS scavenger N-acetylcysteine (NAC) and MAPK inhibitors inhibited zeaxanthin-induced apoptosis, and under the action of zeaxanthin, MAPK regulated NF-κB and STAT3, and reduced their protein expression levels. Conclusion Zeaxanthin has a potential effect against gastric cancer cells through the ROS-mediated MAPK, AKT, NF-κB, and STAT3 signaling pathways, and it is expected to become a new drug for the treatment of human gastric cancer.

Zeaxanthin-Rich Extract from Superfood Lycium barbarum Selectively Modulates the Cellular Adhesion and MAPK Signaling in Melanoma versus Normal Skin Cells In Vitro

“…The increase of phosphorilated JNK, ERK1/2 or p38 membrane expression could lead to an augmented pro-oxidative process inside the tumor cells, detrimental to the survival of tumor cells. Zeaxanthin was able to regulate the increase of JNK and p38 expression in gastric tumor cells through the increase of ROS levels [ 59 ], and this confirms our hypothesis. Overall, the effect of 1 and 2 on A375 melanoma cells in vitro raises questions about the opportunity of their employment as antitumor agents, and downstream effects of these pathways need to be explored as well.…”

Development of Corn-Derived Nanoparticles as Mass-Producible Bionanoparticles with Anticancer Activity

“…epNPs have been reported to contain various biologically active molecules [13,14,16,17]. Lutein and zeaxanthin, the xanthophylls present in corn [28,29], are known to exhibit antitumor effects through regulation of cell cycle or cell apoptosis [42][43][44]. It has been reported that zeaxanthin induced cell cycle arrest at the G2/M phase and apoptosis through the ROS-mediated MAPK, AKT, NF-κB, and STAT3 signaling pathways [43].…”

Eupafolin Induces Apoptosis and Autophagy of Breast Cancer Cells Through PI3K/AKT, MAPKs and NF-κB Signaling Pathways

“…Moreover, the expressions of Cyclins, and CDKs are related to cell cycle [18]. For example, The down-regulation of CDK2, CDK4 and Cyclin B1 can be inhibited by the development of breast cancer [19].…”