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 A Novel Methoxybenzyl 5-Nitroacridone Derivative Effectively Triggers G1 Cell Cycle Arrest in Chronic Myelogenous Leukemia K562 Cells by Inhibiting CDK4/6-Mediated Phosphorylation of Rb

2020 ◽  
Vol 21 (14) ◽  
pp. 5077
Author(s):  
Bin Zhang ◽  
Ting Zhang ◽  
Tian-Yi Zhang ◽  
Ning Wang ◽  
Shan He ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chronic Myeloid Leukemia ◽  
Cell Cycle Arrest ◽  
Chronic Myelogenous Leukemia ◽  
Myeloid Leukemia ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
G1 Phase ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

Chronic myeloid leukemia (CML) is a malignant tumor caused by the abnormal proliferation of hematopoietic stem cells. Among a new series of acridone derivatives previously synthesized, it was found that the methoxybenzyl 5-nitroacridone derivative 8q has nanomolar cytotoxicity in vitro against human chronic myelogenous leukemia K562 cells. In order to further explore the possible anti-leukemia mechanism of action of 8q on K562 cells, a metabolomics and molecular biology study was introduced. It was thus found that most of the metabolic pathways of the G1 phase of K562 cells were affected after 8q treatment. In addition, a concentration-dependent accumulation of cells in the G1 phase was observed by cell cycle analysis. Western blot analysis showed that 8q significantly down-regulated the phosphorylation level of retinoblastoma-associated protein (Rb) in a concentration-dependent manner, upon 48 h treatment. In addition, 8q induced K562 cells apoptosis, through both mitochondria-mediated and exogenous apoptotic pathways. Taken together, these results indicate that 8q effectively triggers G1 cell cycle arrest and induces cell apoptosis in K562 cells, by inhibiting the CDK4/6-mediated phosphorylation of Rb. Furthermore, the possible binding interactions between 8q and CDK4/6 protein were clarified by homology modeling and molecular docking. In order to verify the inhibitory activity of 8q against other chronic myeloid leukemia cells, KCL-22 cells and K562 adriamycin-resistant cells (K562/ADR) were selected for the MTT assay. It is worth noting that 8q showed significant anti-proliferative activity against these cell lines after 48 h/72 h treatment. Therefore, this study provides new mechanistic information and guidance for the development of new acridones for application in the treatment of CML.

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
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