scholarly journals The effect of GSK-3β in arsenic-induced apoptosis of malignant tumor cells: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Xin Gao ◽  
Bin Deng ◽  
Shanshan Ran ◽  
Shugang Li
Keyword(s):  
Tumor Cell ◽  
Malignant Tumor ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Meta Analysis ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Tumor Cell Apoptosis ◽  
Mitochondrial Apoptosis Pathway ◽  
Gsk 3Β

Abstract Purpose: Arsenic has been reported to induce apoptosis in malignant tumor cells, therefore, it may be regarded as a treatment for some cancers. The mitochondrial apoptosis pathway, mediated by GSK-3β, plays an important role in tumor cell apoptosis. Nonetheless, the regulation of GSK-3β by arsenic remains controversial. Materials and Methods: We included 19 articles, which conducts the role of GSK-3β in the process of arsenic-induced tumor cell apoptosis by the meta-analysis. Results: Compared with the control group, the expression of GSK-3β (SMD=-0.92,95% CI (-1.78,-0.06)), p-Akt (SMD=-5.46,95% CI (-8.67,-2.24)) were reduced in the arsenic intervention group. Meanwhile, the combined treatment of arsenic and Akt agonist can inhibit the expression of p-GSK-3β. Using the dose and time subgroup analysis, it was shown that the low-dose and sub-chronic arsenic exposure could inhibit the expression of p-Akt (P<0.05). In the subgroup analysis of GSK-3β sites, arsenic could inhibit p-Akt and GSK-3β (Ser9) (SMD =-0.95, 95% CI (-1.56,-0.33)). There was a dose-related effect seen between arsenic (≤8 μmol/L) and p-GSK-3β, and the expression of p-GSK-3β was gradually followed by the arsenic dose. When arsenic acted on GSK-3β (ser9), the expression of Mcl-1 and pro-caspase-3 were dropped, while the loss rate of mitochondrial membrane potential and cleaved-caspase-3 were increased significantly (P<0.05). Conclusion: This study revealed that arsenic could inhibit the expression of GSK-3β (Ser9) and then induce tumor cell apoptosis. It might be correlated with arsenic inhibiting p-Akt, down-regulating GSK-3β, and triggering the Mcl-1-mediated mitochondrial apoptosis pathway.

scholarly journals Gan-Qing-Ning Formula Inhibits the Growth of Hepatocellular Carcinoma by Promoting Apoptosis and Inhibiting Angiogenesis in H22 Tumor-Bearing Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Fan-Yan Zeng ◽  
Kai-Li Zhao ◽  
Le-Zhen Lin ◽  
Ying Deng ◽  
Si Qin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Effect ◽  
Caspase 3 ◽  
Tumor Tissue ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Expression Levels ◽  
Mitochondrial Apoptosis Pathway ◽  
Tumor Bearing ◽  
Mrna Expression Levels

Objective. Gang-Qing-Ning (GQN) is a traditional Chinese medicine formula that has been used in the treatment of hepatocellular carcinoma (HCC) in the folk population for decades. However, scientific validation is still necessary to lend credibility to the traditional use of GQN against HCC. This study investigates the antitumor effect of GQN on H22 tumor-bearing mice and its possible mechanism. Methods. Fifty H22 tumor-bearing mice were randomly assigned to five groups. Three groups were treated with high, medium, and low dosages of GQN (27.68, 13.84, and 6.92 g/kg, respectively); the positive control group was treated with cytoxan (CTX) (20 mg/kg) and the model group was treated with normal saline. After 10 days’ treatment, the tumor inhibitory rates were calculated. Pathological changes in tumor tissue were observed, and the key proteins and genes of the mitochondrial apoptosis pathway were measured, as well as the mRNA expression levels of VEGF in tumor tissue. Results. The tumor inhibitory rates of high, medium, and low dosages of GQN groups were 47.39%, 38.26%, and 22.17%, respectively. The high dosage of the GQN group significantly increased the protein and mRNA expression levels of Bax, Cyt-C, and cleaved Caspase 3 (or Caspase 3) (P<0.01) but decreased the expression levels of Bcl-2, VEGF, and microvessel density (MVD) (P<0.01). Conclusions. The high dosage of GQN can significantly inhibit the tumor growth in H22 tumor-bearing mice. It exerts the antitumor effect by enhancing proapoptotic factors and inhibiting the antiapoptotic factor of the mitochondrial apoptosis pathway and inhibiting tumor angiogenesis.

scholarly journals Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Linyan Lv ◽  
Yajie Chang ◽  
Yanqing Li ◽  
Haicheng Chen ◽  
Jiahui Yao ◽  
...  
Keyword(s):  
Leydig Cell ◽  
Cell Apoptosis ◽  
Mitochondrial Dynamics ◽  
Reproductive Toxicity ◽  
Mitochondrial Apoptosis ◽  
Mitochondrial Dynamic ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Triptolide is widely used in the clinical treatment of various diseases. Side effects, including reproductive toxicity to male patients, limit its application. However, no detailed mechanisms or potential intervention targets have been reported. In this study, we show that triptolide activated the mitochondrial apoptosis pathway in rat testicular Leydig cells and induced apoptosis both in vivo and in vitro, which may cause hypoleydigism and impair spermatogenesis. Mechanistically, triptolide-induced dynamin-related protein 1 (Drp1) overexpression, which interfered with mitochondrial dynamic stability to activate the mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, partially reversed the mitochondrial dynamic disturbance and rat testicular Leydig cell apoptosis induced by triptolide. Inhibiting Drp1 over-activation may be a new strategy for mitigating the reproductive toxicity of triptolide.

Selenium deficiency induces duodenal villi cell apoptosis via an oxidative stress-induced mitochondrial apoptosis pathway and an inflammatory signaling-induced death receptor pathway

Metallomics ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1390-1400 ◽  
Author(s):  
Jianfa Wang ◽  
Zhe Liu ◽  
Xianjing He ◽  
Shuai Lian ◽  
Jianbin Liang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Trace Element ◽  
Cell Apoptosis ◽  
Death Receptor ◽  
Selenium Deficiency ◽  
Mitochondrial Apoptosis ◽  
Inflammatory Signaling ◽  
Apoptosis Pathway ◽  
Death Receptor Pathway ◽  
Mitochondrial Apoptosis Pathway

Selenium is an important nutritional trace element possessing antioxidant and anti-apoptotic properties in intestinal.

scholarly journals Ivermectin has New Application in Inhibiting Colorectal Cancer Cell Growth

2021 ◽  
Vol 12 ◽  
Author(s):  
Shican Zhou ◽  
Hang Wu ◽  
Wenjuan Ning ◽  
Xiao Wu ◽  
Xiaoxiao Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Annexin V ◽  
Optical Microscope ◽  
Dependent Manner ◽  
Mechanism Analysis ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway

Colorectal cancer (CRC) is the third most common cancer worldwide and still lacks effective therapy. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. However, whether ivermectin affects CRC is still unclear. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. We used CCK-8 assay to determine the cell viability, used an optical microscope to measure cell morphology, used Annexin V-FITC/7-AAD kit to determine cell apoptosis, used Caspase 3/7 Activity Apoptosis Assay Kit to evaluate Caspase 3/7 activity, used Western blot to determine apoptosis-associated protein expression, and used flow cytometry and fluorescence microscope to determine the reactive oxygen species (ROS) levels and cell cycle. The results demonstrated that ivermectin dose-dependently inhibited colorectal cancer SW480 and SW1116 cell growth, followed by promoting cell apoptosis and increasing Caspase-3/7 activity. Besides, ivermectin upregulated the expression of proapoptotic proteins Bax and cleaved PARP and downregulated antiapoptotic protein Bcl-2. Mechanism analysis showed that ivermectin promoted both total and mitochondrial ROS production in a dose-dependent manner, which could be eliminated by administering N-acetyl-l-cysteine (NAC) in CRC cells. Following NAC treatment, the inhibition of cell growth induced by ivermectin was reversed. Finally, ivermectin at low doses (2.5 and 5 µM) induced CRC cell arrest. Overall, ivermectin suppressed cell proliferation by promoting ROS-mediated mitochondrial apoptosis pathway and inducing S phase arrest in CRC cells, suggesting that ivermectin might be a new potential anticancer drug therapy for human colorectal cancer and other cancers.

scholarly journals Protective Effect of N-Acetylcysteine against Oxidative Stress Induced by Zearalenone via Mitochondrial Apoptosis Pathway in SIEC02 Cells

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 407 ◽  
Author(s):  
Jingjing Wang ◽  
Mengmeng Li ◽  
Wei Zhang ◽  
Aixin Gu ◽  
Jiawen Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Messenger Rna ◽  
Caspase 3 ◽  
Intestinal Epithelial ◽  
Mitochondrial Apoptosis ◽  
Caspase 9 ◽  
Treatment Results ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Small Intestinal

Zearalenone (ZEN), a nonsteroidal estrogen mycotoxin, is widely found in feed and foodstuffs. Intestinal cells may become the primary target of toxin attack after ingesting food containing ZEN. Porcine small intestinal epithelial (SIEC02) cells were selected to assess the effect of ZEN exposure on the intestine. Cells were exposed to ZEN (20 µg/mL) or pretreated with (81, 162, and 324 µg/mL) N-acetylcysteine (NAC) prior to ZEN treatment. Results indicated that the activities of glutathione peroxidase (Gpx) and glutathione reductase (GR) were reduced by ZEN, which induced reactive oxygen species (ROS) and malondialdehyde (MDA) production. Moreover, these activities increased apoptosis and mitochondrial membrane potential (ΔΨm), and regulated the messenger RNA (mRNA) expression of Bax, Bcl-2, caspase-3, caspase-9, and cytochrome c (cyto c). Additionally, NAC pretreatment reduced the oxidative damage and inhibited the apoptosis induced by ZEN. It can be concluded that ZEN-induced oxidative stress and damage may further induce mitochondrial apoptosis, and pretreatment of NAC can degrade this damage to some extent.

scholarly journals Taxifolin protects rat against myocardial ischemia/reperfusion injury by modulating the mitochondrial apoptosis pathway

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6383 ◽  
Author(s):  
Zhenqiu Tang ◽  
Chunjuan Yang ◽  
Baoyan Zuo ◽  
Yanan Zhang ◽  
Gaosong Wu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Myocardial Apoptosis ◽  
Cyt C ◽  
Myocardial Ischemia Reperfusion

Background Taxifolin (TAX), is an active flavonoid, that plays an underlying protective role on the cardiovascular system. This study aimed to evaluate its effect and potential mechanisms on myocardial ischemia/reperfusion (I/R) injury. Methods Healthy rat heart was subjected to I/R using the Langendorff apparatus. Hemodynamic parameters, including heart rate, left ventricular developed pressure (LVDP), maximum/minimum rate of the left ventricular pressure rise (+dp/dtmax and −dp/dtmin) and rate pressure product (RPP) were recorded during the perfusion. Histopathological examination of left ventricular was measured by hematoxylin-eosin (H&E) staining. Creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities in the effluent perfusion, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in the tissue were assayed. Apoptosis related proteins, such as B-cell lymphoma-2 (Bcl-2), Bcl2-associated X (Bax), and cytochrome c (Cyt-c) were also assayed by ELISA. Western blot was employed to determine apoptosis-executive proteins, including caspase 3 and 9. Transferase-mediated dUTP-X nick end labeling assay was performed to evaluate the effect TAX on myocardial apoptosis. Results Taxifolin significantly improved the ventricular functional recovery, as evident by the increase in LVDP, +dp/dtmax, −dp/dtmin and RPP, the levels of SOD, GSH-PX were also increased, but those of LDH, CK-MB, and MDA were decreased. Furthermore, TAX up-regulated the Bcl-2 protein level but down-regulated the levels of Bax, Cyt-c, caspase 3 and 9 protein, thereby inhibits the myocardial apoptosis. Discussion Taxifolin treatment remarkably improved the cardiac function, regulated oxidative stress and attenuated apoptosis. Hence, TAX has a cardioprotective effect against I/R injury by modulating mitochondrial apoptosis pathway.

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