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.

10‐Hydroxy‐2‐decenoic acid (10‐HDA), also known as royal jelly acid, has a variety of physiological functions, and recent studies have shown that it also has anticancer effects. However, its anticancer mechanisms have not been clearly defined. In this study, we investigated the underlying mechanisms of 10‐HDA in A549 human lung cancer cells. We used Cell Counting Kit‐8 assay, scratch wound healing assay, flow cytometry, and western blot analysis to investigate its apoptotic effects and underlying mechanism. Our results showed that 10‐HDA inhibited the proliferation of three types of human lung cancer cells and had no significant toxic effects on normal cells. Accompanying reactive oxygen species (ROS), 10‐HDA induced A549 cell apoptosis by regulating mitochondrial‐associated apoptosis, and caused cell cycle arrest at the G0/G1 phase in a time‐dependent manner. Meanwhile, 10‐HDA also regulated mitogen‐activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF‐κB) signaling pathways by increasing the expression levels of phosphorylated c‐Jun N‐terminal kinase, p‐p38, and I‐κB, and additionally, by decreasing the expression levels of phosphorylated extracellular signal‐regulated kinase, p‐STAT3, and NF‐κB. These effects were blocked by MAPK inhibitors and N‐acetyl‐L‐cysteine. Furthermore, 10‐HDA inhibited cell migration by regulating transforming growth factor beta 1 (TGF‐β1), SNAI1, GSK‐3β, E‐cadherin, N‐cadherin, and vimentin. Taken together, the results of this study showed that 10‐HDA induced cell cycle arrest and apoptosis in A549 human lung cancer cells through ROS‐mediated MAPK, STAT3, NF‐κB, and TGF‐β1 signaling pathways. Therefore, 10‐HDA may be a potential therapy for human lung cancer.

Background: 18β-glycyrrhetinic acid (18β-Gly), which is extracted from licorice root, has various pharmacological properties; however, its anti-cancer effects on lung cancer cells have not been fully established. Purpose: In this study, we investigated the underlying molecular mechanisms of 18β-Gly. Results: Our results showed that 18β-Gly had significant cytotoxic effects and no apparent side effects. 18β-Gly induced mitochondria-dependent apoptosis of A549 lung cancer cells. In addition, after treatment with 18β-Gly, intracellular reactive oxygen species (ROS) levels were significantly increased, and G2/M cell cycle arrest and inhibition of cell migration were induced via the mitogen-activated protein kinase (MAPK)/signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa (NF-κB) signaling pathways. After pretreatment with the ROS scavenger N-acetyl-L-cysteine or MAPK inhibitors, the expression levels of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase, inhibitor of nuclear factor kappa B, cleaved caspase-3 (cle-cas-3), cleaved poly (ADP ribose) polymerase (cle-PARP), p-p53, p27, p21, and E-cadherin were decreased; and levels of phosphorylated extracellular signal-regulated kinase, p-STAT3, NF-κB, Bcl-2, cyclin B1, cyclase-dependent kinase 1/2 (CDK1/2), N-cadherin, vimentin, and snail homolog 1 (SNAI 1) were increased. In addition, the percentage of cells in the G2/M phase was decreased, and inhibition of migration was reduced. Conclusion: In summary, 18β-Gly induced apoptosis and G2/M cell cycle arrest and inhibited migration via the ROS/MAPK/STAT3/NF-κB signaling pathways in A549 lung cancer cells. Therefore, 18β-Gly is a novel promising candidate for the treatment of lung cancer.