scholarly journals Ropivacaine induces cell cycle arrest in the G0/G1 phase and apoptosis of PC12 cells via inhibiting mitochondrial STAT3 translocation

2021 ◽  
Author(s):  
Lian Zeng ◽  
Zhen Zhang ◽  
Fuyu Zhang ◽  
Huaxian Chen ◽  
Ying Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Spinal Cord ◽  
Cell Cycle Arrest ◽  
Pc12 Cells ◽  
Neuroprotective Effect ◽  
G1 Phase ◽  
Upstream Gene ◽  
Mitochondrial Translocation ◽  
Cycle Arrest ◽  
Induced Apoptosis

Abstract STAT3 has neuroprotective effect via non-canonical activation and mitochondrial translocation, but its effects on ropivacaine-induced neurotoxicity remain unclear. Our previous study revealed that apoptosis was an important mechanism of ropivacaine-induced neurotoxicity, this study is to illustrate the relationship between STAT3 with ropivacaine-induced apoptosis. Those results showed that ropivacaine treatment decreased cell viability, induced cell cycle arrest in the G0/G1 phase, apoptosis, oxidative stress, and mitochondrial dysfunction in PC12 cells. Besides, ropivacaine decreased the phosphorylated levels of STAT3 at Ser727 and downregulated the expression of STAT3 upstream gene IL-6. The mitochondrial translocation of STAT3 was also hindered by ropivacaine. To further illustrate the connection of STAT3 protein structure with ropivacaine, the autodock-vina was used to examine the interaction between STAT3 and ropivacaine, and the results showed that ropivacaine could bind to STAT3’s proline site and other sites. In addition, the activator and inhibitor of mitoSTAT3 translocation were used to demonstrate it was involved in ropivacaine-induced apoptosis, the results showed that enhancing the mitochondrial STAT3 translocation could prevent ropivacaine-induced apoptosis. Finally, the expression of p-STAT3 and the levels of apoptosis in the spinal cord were also detected, the results were consistent with the cell experiment, ropivacaine decreased the expression of p-STAT3 protein and increased the levels of apoptosis in the spinal cord. We demonstrated that ropivacaine induced apoptosis by inhibiting the phosphorylation of STAT3 at Ser727 and the mitochondrial STAT3 translocation. This effect was reversed by the activation of the mitochondrial STAT3 translocation.

JNK/c-Jun Is Required for HMC-1 Cell Proliferation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4439-4439
Author(s):  
Bin Wang ◽  
Junichi Tsukada ◽  
Takehiro Higashi ◽  
Takamitsu Mizobe ◽  
Ai Matsuura ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Mast Cells ◽  
Cell Cycle Arrest ◽  
Caspase 3 ◽  
Cyclin D3 ◽  
G1 Phase ◽  
Caspase 9 ◽  
Cycle Arrest ◽  
Induced Apoptosis

Abstract Activation of c-jun N-terminal kinase (JNK) through c-kit-mediated phosphatidylinositol 3 (PI3) and Src kinase pathways plays an important role in cell proliferation and survival in mast cells. Gain-of-function mutations in c-kit are found in several human neoplasms. Constitutive activation of c-kit has been observed in human mastocytosis, acute myeloid leukemia, lymphoma, germ tumor and gastrointestinal stromal tumor. In the present study, we demonstrate that an anthrapyrazole SP600125, a reversible ATP-competitive inhibitor of JNK inhibits proliferation of human HMC-1 mast cells expressing constitutively activated c-kit mutant. We found that JNK/c-Jun was constitutively activated in HMC-1 cells without stimulation. When spontaneous activation of JNK/c-Jun was inhibited by treatment with SP600125, cell proliferation was suppressed. The concentration which effectively inhibited JNK/c-Jun activity in our experiment had no effect on SCF-induced phosphorylation of Akt or Erk, suggesting that SP600125 specifically inhibited JNK/c-Jun activity in HMC-1 cells. Moreover, we demonstrated that SP600125 induced HMC-1 cell apoptosis in dose- and time-dependent manner. Caspase-3 and PARP were cleaved as early as 12 h after treatment with SP600125, but caspase-9 was not. Also, cell cycle arrest in G1 phase was observed in SP600125 treated cells. Thus, the inhibitory effect of SP600125 on cell proliferation was associated with cell cycle arrest at the G1 phase and apoptosis accompanied by cleavage of caspase-3 and PARP. Caspase-3 inhibitor Z-DEVD-FMK almost completely inhibited SP600125-induced apoptosis of HMC-1 cells. In contrast, caspase-9 inhibitor Z-LEHD-FMK failed to block SP600125-induced apoptosis, suggesting that apoptosis induced by SP600125 was caspase-3 dependent. Following SP600125 treatment, down-regulation of cyclin D3 protein expression, but not p53 was also observed. Take together, JNK/c-Jun is essential for proliferation and survival of HMC-1 cells. The results obtained from the present study suggest the possibility that JNK/c-Jun may be a therapeutic target in diseases associated with c-kit mutant.

scholarly journals Effects of annexin A1 on apoptosis and cell cycle arrest in human leukemic cell lines

2019 ◽  
Vol 69 (1) ◽  
pp. 75-86 ◽  
Author(s):  
Affidah Sabran ◽  
Endang Kumolosasi ◽  
Ibrahim Jantan
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Leukemic Cell ◽  
Jurkat Cells ◽  
G1 Phase ◽  
U937 Cells ◽  
Annexin A1 ◽  
Leukemic Cell Lines ◽  
Cycle Arrest ◽  
Induced Apoptosis

Abstract Recent studies suggest that annexin A1 (ANXA1) promotes apoptosis in cancerous cells. This study aims to investigate the effects of ANXA1 on apoptosis and cell cycle arrest in K562, Jurkat and U937 cells and peripheral blood mononu-clear cells (PBMC). Cells were treated with ANXA1 and cyclophosphamide prior to flow cytometry analysis for apoptosis and cell cycle arrest induction. At 2.5µM, ANXA1 induced significant apoptosis in K562 (p ≤ 0.001) and U937 (p ≤ 0.05) cells, with EC50 values of 3.6 and 3.8 µM, respectively. In Jurkat cells, induction was not significant (EC50, 17.0 µM). No significant apoptosis induction was observed in PBMC. ANXA1 caused cycle arrest in the G0/G1 phase in K562 and U937 cells with p ≤ 0.001 for both, and (p ≤ 0.01) for Jurkat cells. ANXA1 induced apoptosis and cycle arrest in the G0/G1 phase in K562 and U937 cells, causing only cell cycle arrest in Jurkat cells.

Polycystin-1 induced apoptosis and cell cycle arrest in G0/G1 phase in cancer cells

2008 ◽  
Vol 32 (4) ◽  
pp. 427-435 ◽  
Author(s):  
Rong Zheng ◽  
Zheng Zhang ◽  
Xiaoyan Lv ◽  
JunMing Fan ◽  
Ye Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
G1 Phase ◽  
Cycle Arrest ◽  
Induced Apoptosis

scholarly journals Jellyfish extract induces apoptotic cell death through the p38 pathway and cell cycle arrest in chronic myelogenous leukemia K562 cells

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e2895 ◽  
Author(s):  
Sun-Hyung Ha ◽  
Fansi Jin ◽  
Choong-Hwan Kwak ◽  
Fukushi Abekura ◽  
Jun-Young Park ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Chronic Myelogenous Leukemia ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
G1 Phase ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Induced Apoptosis ◽  
Cancer Activity

Jellyfish species are widely distributed in the world’s oceans, and their population is rapidly increasing. Jellyfish extracts have several biological functions, such as cytotoxic, anti-microbial, and antioxidant activities in cells and organisms. However, the anti-cancer effect of Jellyfish extract has not yet been examined. We used chronic myelogenous leukemia K562 cells to evaluate the mechanisms of anti-cancer activity of hexane extracts from Nomura’s jellyfish in vitro. In this study, jellyfish are subjected to hexane extraction, and the extract is shown to have an anticancer effect on chronic myelogenous leukemia K562 cells. Interestingly, the present results show that jellyfish hexane extract (Jellyfish-HE) induces apoptosis in a dose- and time-dependent manner. To identify the mechanism(s) underlying Jellyfish-HE-induced apoptosis in K562 cells, we examined the effects of Jellyfish-HE on activation of caspase and mitogen-activated protein kinases (MAPKs), which are responsible for cell cycle progression. Induction of apoptosis by Jellyfish-HE occurred through the activation of caspases-3,-8 and -9 and phosphorylation of p38. Jellyfish-HE-induced apoptosis was blocked by a caspase inhibitor, Z-VAD. Moreover, during apoptosis in K562 cells, p38 MAPK was inhibited by pretreatment with SB203580, an inhibitor of p38. SB203580 blocked jellyfish-HE-induced apoptosis. Additionally, Jellyfish-HE markedly arrests the cell cycle in the G0/G1 phase. Therefore, taken together, the results imply that the anti-cancer activity of Jellyfish-HE may be mediated apoptosis by induction of caspases and activation of MAPK, especially phosphorylation of p38, and cell cycle arrest at the Go/G1 phase in K562 cells.

scholarly journals Ropivacaine Induce G0 / G1 Phase Cell Cycle Arrest and Apoptosis of PC12 Cells Via Inhibiting Mitochondrial STAT3 Translocation

2021 ◽  
Author(s):  
Lian Zeng ◽  
Zhen Zhang ◽  
Fuyu Zhang ◽  
Chenguang Liu ◽  
Jiafeng He ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Phase Cell ◽  
G1 Phase ◽  
Neuroprotective Effects ◽  
Mitochondrial Translocation ◽  
Cycle Arrest ◽  
Mitochondrial Functions ◽  
Induced Apoptosis ◽  
The Relationship ◽  
Transcription 3

Abstract Signal transducer and activator of transcription 3 (STAT3) has been shown to have neuroprotective effects via the non-canonical activation and mitochondrial translocation, but its effect on ropivacaine induced neurotoxicity is unclear. Our previous studies have revealed that apoptosis was an important mechanism of ropivacaine induced neurotoxicity, so this study is to explore the relationship between STAT3 with ropivacaine induced apoptosis. Our results showed that ropivacaine decreased PC12 cell viability, arrested the cells in the G0 / G1 phase, induced cell apoptosis and oxidative stress, and damaged mitochondrial functions. In addition, the serine727 (Ser727) phosphate activation of STAT3 was inhibited by ropivacaine. Ropivacaine decreased the p-STAT3 (Ser727) expression in the mitochondria, and increased p-STAT3 (Ser727) expression in the cytoplasm, so that it inhibited mitochondrial STAT3 translocation. To explore the potential connection between STAT3 with ropivacaine, the autodock-vina was used to examine the interaction between STAT3 and ropivacaine, and results showed that ropivacaine could bind to STAT3. Furthermore, the apoptosis of the spinal cord was increased and the p-STAT3 (Ser727) expression in the spinal cord was reduced after ropivacaine treatment. our findings illustrated that ropivacaine induced neurotoxicity by increasing the apoptotic levels, the activation and mitochondrial translocation of STAT3 were inhibited by ropivacaine. There may be an internal connection between these phenomena.

Synergistic Effect of α-Solanine and Cisplatin Induces Apoptosis and Enhances Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells

2020 ◽  
Vol 19 (18) ◽  
pp. 2197-2210 ◽  
Author(s):  
Sherien M. El-Daly ◽  
Shaimaa A. Gouhar ◽  
Amira M. Gamal-Eldeen ◽  
Fatma F. Abdel Hamid ◽  
Magdi N. Ashour ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Synergistic Effect ◽  
Cell Cycle Arrest ◽  
Combination Treatment ◽  
Carcinoma Cells ◽  
Cell Growth Inhibition ◽  
Cycle Arrest ◽  
Induced Apoptosis ◽  
Human Hepatocellular Carcinoma Cells

Aim: The clinical application of cisplatin is limited by severe side effects associated with high applied doses. The synergistic effect of a combination treatment of a low dose of cisplatin with the natural alkaloid α-solanine on human hepatocellular carcinoma cells was evaluated. Methods: HepG2 cells were exposed to low doses of α-solanine and cisplatin, either independently or in combination. The efficiency of this treatment modality was evaluated by investigating cell growth inhibition, cell cycle arrest, and apoptosis enhancement. Results: α-solanine synergistically potentiated the effect of cisplatin on cell growth inhibition and significantly induced apoptosis. This synergistic effect was mediated by inducing cell cycle arrest at the G2/M phase, enhancing DNA fragmentation and increasing apoptosis through the activation of caspase 3/7 and/or elevating the expression of the death receptors DR4 and DR5. The induced apoptosis from this combination treatment was also mediated by reducing the expression of the anti-apoptotic mediators Bcl-2 and survivin, as well as by modulating the miR-21 expression. Conclusion: Our study provides strong evidence that a combination treatment of low doses of α-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.

scholarly journals Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 302 ◽  
Author(s):  
Xin Zhang ◽  
Yao Qin ◽  
Zhaohai Pan ◽  
Minjing Li ◽  
Xiaona Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Protein Expression ◽  
Cell Cycle Arrest ◽  
Phase Cell ◽  
G1 Phase ◽  
Therapeutic Effects ◽  
Human Gastric Cancer ◽  
Expression Levels ◽  
Cycle Arrest

The main chemical component of cannabis, cannabidiol (CBD), has been shown to have antitumor properties. The present study examined the in vitro effects of CBD on human gastric cancer SGC-7901 cells. We found that CBD significantly inhibited the proliferation and colony formation of SGC-7901 cells. Further investigation showed that CBD significantly upregulated ataxia telangiectasia-mutated gene (ATM) and p53 protein expression and downregulated p21 protein expression in SGC-7901 cells, which subsequently inhibited the levels of CDK2 and cyclin E, thereby resulting in cell cycle arrest at the G0–G1 phase. In addition, CBD significantly increased Bax expression levels, decreased Bcl-2 expression levels and mitochondrial membrane potential, and then upregulated the levels of cleaved caspase-3 and cleaved caspase-9, thereby inducing apoptosis in SGC-7901 cells. Finally, we found that intracellular reactive oxygen species (ROS) increased after CBD treatment. These results indicated that CBD could induce G0–G1 phase cell cycle arrest and apoptosis by increasing ROS production, leading to the inhibition of SGC-7901 cell proliferation, thereby suggesting that CBD may have therapeutic effects on gastric cancer.

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