Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT signaling pathways.
Ontology highlight
ABSTRACT:
SUBMITTER: Hao W
PROVIDER: S-EPMC4434846 | biostudies-other | 2015
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The p38 MAPKs play important roles in the regulation of balance between cell survival and cell death on the development of various cancers. However, the roles of p38 MAPKs regulating apoptotic effects on Leydig tumor cells remain unclear. In the present study, we showed that cordycepin (3'-deoxyadenosine) selectively induced apoptosis in MA-10 mouse Leydig tumor cells through regulating the p38 MAPK and PI3K/AKT signaling pathways. Cordycepin reduced viability in MA-10, TM4, and NT2/D1 cells, but not cause cell death of primary mouse Leydig cells on moderate concentration. Cordycepin increased reactive oxygen species (ROS) levels, which is associated with the induction of apoptosis as characterized by positive Annexin V binding, activation of caspase-3, and cleavage of PARP. Inhibition of p38 MAPKs activity by SB203580 significantly prevented cordycepin-induced apoptosis in MA-10 cells. Co-treatment with wortmannin or the autophagy inhibitor 3-methyladenine (3-MA) elevated levels of apoptosis in cordycepin-treated MA-10 cells. Moreover, cordycepin activated p53, p21 and TGFß; and downregulated CDK2. The antitumour activity of cordycepin-treated MA-10 cells was significantly distinct in severe combined immunodeficiency (SCID) mice in vivo. These results suggested that cordycein is a highly selective treatment to induce MA-10 cells apoptosis via p38 MAPKs signaling.
| S-EPMC4548195 | biostudies-literature
Project description:Eupafolin is a flavonoid that can be extracted from common sage. Previous studies have reported that Eupafolin has antioxidant, anti-inflammatory and anti-tumor properties. However, no studies have investigated the role of Eupafolin in breast cancer. Herein, we investigated the effect of Eupafolin on two human breast cancer cell lines, as well as its potential mechanism of action. Next, the data showed that proliferation, migration and invasion ability of breast cancer cells that were treated with Eupafolin was significantly reduced, while the apoptosis rate was significantly increased. In addition, Eupafolin treatment caused breast cancer cell proliferation to be blocked in the S phase. Moreover, Eupafolin significantly induced autophagy in breast cancer cells, with an increase in the expression of LC3B-II. PI3K/AKT, MAPKs and NF-κB pathways were significantly inhibited by Eupafolin treatment. Additionally, 3-MA (a blocker of autophagosome formation) significantly reduced Eupafolin-induced activation of LC3B-II in breast cancer cells. Furthermore, Eupafolin displayed good in vitro anti-angiogenic activity. Additionally, anti-breast cancer activity of Eupafolin was found to be partially mediated by Cav-1. Moreover, Eupafolin treatment significantly weakened carcinogenesis of MCF-7 cells in nude mice. Therefore, this data provides novel directions on the use of Eupafolin for treatment of breast cancer.
| S-EPMC8563970 | biostudies-literature
Project description:BackgroundTo explore the mechanism of OIP5-AS1/CD147/TRPM7 axis to gastric cancer (GC) metastasis.MethodsBioinformatic analysis was performed to pick up the candidate genes associated with regulation GC metastasis. Using GC cell lines, AGS and MKN-45 as research objects, identify the effect of candidate genes on GC metastasis, judge cell proliferation status by MTT assay and cell clone number, and detect cell migration by Transwell and Wound-healing assay. The molecular mechanism of CD147/OIP5/TRPM7 axis regulating GC metastasis was further explored by RNA sequencing. The key signaling pathways were subsequently verified by flow cytometry and WB.ResultsBioinformatic analysis suggested OIP5-AS1/CD147/TRPM7 axis may be involving in GC metastasis. The RNA interference experiment proved that after gene interference, the proliferation ability of GC cells decreased significantly (P<0.05), which was manifested in the reduction of the number of cell clones. In addition, the migration ability of GC cells was also affected, which was based on the results of Wound Healing (P<0.05). CD147, OIP5-AS1 and TRPM7 all have harmful effects on GC cells. The relationship between OIP5-AS1 and CD147/TRPM7 was detected by RNA immunoprecipitation. Moreover, the RNA sequencing data indicated that CD147/OIP5-AS1/TRPM7 may coordinately regulate the PI3K-AKT pathway related to GC cell apoptosis, thereby affecting the proliferation and migration of GC cells. After RNA interference, the level of apoptosis increased both in AGS and MKN-45 cells. Meanwhile, the expression of pro-apoptotic proteins Caspase9 and BAX were up-regulated (P<0.05). In addition, the expression of PI3K and AKT proteins was reduced (P<0.05). The mouse tumorigenesis experiment corroborated the results of the in vitro study.ConclusionOIP5-AS1/CD147/TRPM7 axis reduces GC cell proliferation by regulating apoptosis associated with PI3K-AKT signaling, further affecting cancer metastasis.
| S-EPMC10753821 | biostudies-literature
Project description:Gallbladder cancer (GBC), highly aggressive form of cancer with an extremely poor prognosis, is the most common malignancy of the biliary tract. In this study, we investigated the effects of dioscin (DSN) on human GBC and the potential mechanisms underlying these effects. The results showed that DSN significantly inhibited GBC cell proliferation and migration. Moreover, DSN induced GBC cell apoptosis via mitochondrial dependent apoptotic signalling. Reactive oxygen species (ROS) and glutathione (GSH) levels were measured, and ROS scavengers completely inhibited DSN-induced apoptosis and migration, indicating that ROS play an essential role in GBC progression. Western blot analysis showed that AKT activity was significantly downregulated after DSN treatment, and that inhibition/ectopic expression of AKT enhanced/abolished DSN-induced apoptosis but not migration. Furthermore, we confirmed the relationship between ROS and the PI3K/AKT pathway and found that DSN induced apoptosis by regulating ROS-mediated PI3K/AKT signaling. Taken together, these findings indicate that DSN induces GBC apoptosis through inhibiting ROS-mediated PI3K/AKT signalling.
| S-EPMC5485633 | biostudies-literature
Project description:Context: Cisplatin-based chemotherapy was widely used in treating human malignancies. However, side effects and chemoresistance remains the major obstacle.Objective: To verify whether natural borneol (NB) can enhance cisplatin-induced glioma cell apoptosis and explore the mechanism.Materials and methods: Cytotoxicity of cisplatin and/or NB towards U251 and U87 cells were determined with the MTT assay. Cells were treated with 0.25-80 μg/mL cisplatin and/or 5-80 μM NB for 48 h. The effects of NB and/or cisplatin on apoptosis and cell cycle distribution were quantified by flow cytometric analysis. Protein expression was detected by western blotting. ROS generation was conducted by measuring and visualising an oxidation-sensitive fluorescein DCFH-DA.Results: NB synergistically enhanced the anticancer efficacy of cisplatin in human glioma cells. Co-treatment of 40 μg/mL NB and 40 μg/mL cisplatin significantly inhibited U251 cell viability from 100% to 28.2% and increased the sub-G1 population from 1.4% to 59.3%. Further detection revealed that NB enhanced cisplatin-induced apoptosis by activating caspases and triggering reactive oxygen species (ROS) overproduction as evidenced by the enhancement of green fluorescence intensity from 265% to 645%. ROS-mediated DNA damage was observed as reflected by the activation of ATM/ATR, p53 and histone. Moreover, MAPKs and PI3K/AKT pathways also contributed to co-treatment-induced U251 cell growth inhibition. ROS inhibition by antioxidants effectively improved MAPKs and PI3K/AKT functions and cell viability, indicating that NB enhanced cisplatin-induced cell growth in a ROS-dependent manner.Discussion and conclusions: Natural borneol had the potential to sensitise human glioma cells to cisplatin-induced apoptosis with potential application in the clinic.
| S-EPMC6970185 | biostudies-literature
Project description:BackgroundBreast cancer is the most prevalent cancer among women. In triple-negative breast cancer (TNBC) cells, a novel quinone derivative, coenzyme Q0 (CoQ0), promotes apoptosis and cell-cycle arrest. This study explored the anti-epithelial-mesenchymal transition (EMT) and antimetastatic attributes of CoQ0 in TNBC (MDA-MB-231).MethodsInvasion, as well as MTT assays were conducted. Lipofectamine RNAiMAX was used to transfect cells with β-catenin siRNA. Through Western blotting and RT-PCR, the major signaling pathways' protein expressions were examined, and the biopsied tumor tissues underwent immunohistochemical and hematoxylin and eosin staining as well as Western blotting.ResultsCoQ0 (0.5-2 μM) hindered tumor migration, invasion, and progression. Additionally, it caused MMP-2/- 9, uPA, uPAR, and VEGF downregulation. Furthermore, in highly metastatic MDA-MB-231 cells, TIMP-1/2 expression was subsequently upregulated and MMP-9 expression was downregulated. In addition, CoQ0 inhibited metastasis and EMT in TGF-β/TNF-α-stimulated non-tumorigenic MCF-10A cells. Bioluminescence imaging of MDA-MB-231 luciferase-injected live mice demonstrated that CoQ0 significantly inhibited metastasis of the breast cancer to the lungs and inhibited the development of tumors in MDA-MB-231 xenografted nude mice. Silencing of β-catenin with siRNA stimulated CoQ0-inhibited EMT. Western blotting as well as histological analysis established that CoQ0 reduced xenografted tumor development because apoptosis induction, cell-cycle inhibition, E-cadherin upregulation, β-catenin downregulation, and metastasis and EMT regulatory protein modulation were observed.ConclusionsCoQ0 inhibited the progression of metastasis as well as EMT (in vitro and in vivo). The described approach has potential in treating human breast cancer metastasis.
| S-EPMC6505074 | biostudies-literature
Project description:Liver ischemia/reperfusion (I/R) injury is a common injury after liver transplantation and hepatectomy. Skimmianine (Ski) has antibacterial, antiviral pharmacological effects. However, it is not clear whether Ski has a protective effect against liver I/R injury. In the present study, we established a mouse liver I/R model and an AML12 cell hypoxia-reoxygenation (H/R) model, both pretreated with different concentrations of Ski. Serum transaminase levels, necrotic liver area, cell viability, inflammatory factors, oxidative stress and apoptosis-related levels were measured to assess the protective effect of Ski against liver I/R injury. Western blotting was used to detect apoptosis-related proteins and PI3K-AKT pathway-related proteins. Mice and cells were also treated with PI3K inhibitor LY294002 to assess changes in indicators of liver injury. The results showed that Ski significantly reduced transaminase levels, liver necrosis area, oxidative stress, and apoptosis levels in mice with I/R. Ski also inhibited cell injury and apoptosis after H/R. Moreover, Ski activated phosphorylation of PI3K-AKT pathway-related proteins after liver I/R and cell H/R. Importantly, the PI3K inhibitor LY294002 effectively reversed the alleviation of I/R injury caused by Ski. These results confirm that Ski exerts a protective effect against liver I/R injury through activation of the PI3K-AKT pathway.
| S-EPMC10600244 | biostudies-literature
Project description:BackgroundThe primary objective of this investigation was to assess the impact of pyrroline-5-carboxylate reductase 1 (PYCR1) on the progression of gastric cancer (GC), specifically focusing on tumor growth and metastatic potential.MethodsSurgical specimens from patients with different stages of GC were assayed for PYCR1 expression using immunohistochemistry. PYCR1 expression was manipulated by depletion or overexpression approaches in GC cells, and these cells were applied to explore the functional roles of PYCR1. Expression of apoptosis- and metastasis-related markers was quantified through quantitative real-time PCR and Western blot.ResultsHigher PYCR1 expression was ascertained in surgical specimens from patients with GC as compared to noncancerous adjacent tissues. Additionally, PYCR1 overexpression in GC tissues was linked to adverse clinical outcomes. The depletion of PYCR1 in GC cells resulted in a pronounced reduction in proliferation, the induction of apoptosis, and the attenuation of invasion and metastasis. Conversely, its ectopic expression notably augmented proliferation, restricted apoptosis, and stimulated invasion and metastasis. In addition, the knockdown of PYCR1 resulted in a significant elevation in the activation of caspase 3, a key protein involved in apoptosis. This depletion also led to a decrease in the activation or expression of proteins associated with metastasis, such as phosphorylated (p)-phosphatidylinositol 3-kinase (PI3K), p-AKT serine/threonine kinase (AKT), and snail family transcriptional repressor 1 (Snail). Additionally, it resulted in an upregulation of E-cadherin expression. Conversely, the overexpression of PYCR1 notably increased the levels of p-PI3K, p-AKT, and Snail, while simultaneously reducing E-cadherin expression.ConclusionPYCR1, by activating PI3K/AKT signaling, assumes a crucial role in governing malignant characteristics of GC cells, including proliferation, apoptosis, and metastasis. These findings underscore the promising potential of PYCR1 as a diagnostic biomarker and a target for tailored therapeutic interventions in patients with GC.
| S-EPMC10918153 | biostudies-literature
Project description:Cytokine storm is an important cause of acute respiratory distress syndrome and multiple organ failure. Excessive secretion and accumulation of mucins on the surface of airway cause airway obstruction and exacerbate lung infections. MUC5AC and MUC5B are the main secreted mucins and overexpressed in various inflammatory responses. S-allylmercaptocysteine, a water-soluble organic sulfur compound extracted from garlic, has anti-inflammatory and anti-oxidative effects for various pulmonary diseases. The aim of this work was to investigate the therapeutic effects of SAMC on mucin overproduction and inflammation in 16HBE cells and LPS-induced ARDS mice. Results show that SAMC treatment ameliorated inflammatory cell infiltration and lung histopathological changes in the LPS-induced ARDS mice. SAMC also inhibited the expressions of MUC5AC and MUC5B, decreased the production of pro-inflammatory markers (IL-6, TNF-?, CD86 and IL-12) and increased the production of anti-inflammatory markers (IL-10, CD206 and TGF-?). These results confirm that SAMC had potential beneficial effects on suppressed hyperinflammation and mucin overexpression. Furthermore, SAMC exerted the therapeutic effects through the inhibition of phosphorylation of MAPKs and PI3K-Akt signaling pathways in the 16HBE cells and mice. Overall, our results demonstrate the effects of SAMC on the LPS-induced mucin overproduction and inflammation both in the 16HBE cells and mice.
| S-EPMC7305891 | biostudies-literature
Project description:Metastasis is one of the main causes of mortality in cancer patients. Inotilone, a major component of Inonotus linteus, is a traditional Chinese medical herb. In this study, MTT results showed that inotilone had no obvious cytotoxicity. Animal model results revealed that inotilone suppressed cancer metastatic efficacy. Serum results showed that inotilone reduced the activity of matrix metalloproteinase (MMP)-2 and -9 and tumor necrosis factor alpha (TNF-α) activity as well as NO content. Additionally, inotilone affected MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-2 protein expression and improved the activity of the antioxidant enzymes in the lung tissues of LLC-bearing mice. In addition, cell experimental results showed that inotilone reduced the activity of MMP-2/-9 and inhibited the ability for cellular migration and invasion. Inotilone decreased interleukin (IL)-8 expression in A549 cells. Western blot results revealed that inotilone affected the protein expression of MMPs, nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, anti-oxidant enzymes, mitogen activated protein kinase (MAPK), focal adhesion kinase (FAK), phosphoinositide-3 kinase (PI3K)-AKT, and nuclear factor (NF)κB. Therefore, we propose that inotilone is a potential therapeutic candidate against metastatic lung cancer cells.
| S-EPMC6382761 | biostudies-literature