Propranolol induced apoptosis and autophagy via the ROS/JNK signaling pathway in human ovarian cancer

2020 ◽  
Author(s):  
Shujun Zhao ◽  
Suzhen Fan ◽  
Yanyu Shi ◽  
Hongyan Ren ◽  
Hanqing Hong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Flow Cytometry ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Human Ovarian Cancer ◽  
Dependent Manner ◽  
Flow Cytometry Analysis ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway ◽  
Induced Apoptosis

Abstract Background: Propranolol has a significant anti-cancer effect on various cancers. The present study aimed to investigate the underlying mechanism behind the therapeutic effect of Propranolol on the ovarian cancer.Materials and methods: The effect of Propranolol on cell viability was examined by MTT analysis. Cellular apoptosis was evaluated by flow cytometry analysis. Autophagy was defined by autophagosome observed by confocal microscopy after infected with GFP-LC3 adenovirus. In addition, the expression of marker proteins involved in cell apoptosis, autophagy, and ROS/JNK signaling pathway were estimated by Western Blotting assay.Results: Propranolol significantly reduced the viability of human ovarian cancer cell lines SKOV-3 and A2780 in a dose- and time-dependent manner. Flow cytometry analysis revealed that Propranolol induced the cell cycle arrest at G2/M phase and resulted in apoptosis. Moreover, autophagy inhibitor 3-MA markedly enhanced the Propranolol-induced apoptosis. In addition, reactive oxygen species (ROS) was demonstrated dramatically increased after Propranolol treatment and Propranolol activated the phosphorylation of JNK. What is more, p38 inhibitor SB203580 and JNK inhibitor SP600125 attenuated the upregulated expression of LC3-II and cleaved-caspase-3 by the effect of Propranolol. ROS exclusive inhibitor antioxidant N-acetyl cysteine (NAC) weaken the phosphorylation of JNK proteins induced by Propranolol.Conclusions：In summary, our results suggested that Propranolol induced cell apoptosis and protective autophagy through the ROS/JNK signaling pathway in human ovarian cancer cells.

scholarly journals Propranolol induced apoptosis and autophagy via the ROS/JNK signaling pathway in Human Ovarian Cancer

2020 ◽  
Vol 11 (20) ◽  
pp. 5900-5910
Author(s):  
Shujun Zhao ◽  
Suzhen Fan ◽  
Yanyu Shi ◽  
Hongyan Ren ◽  
Hanqing Hong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Human Ovarian Cancer ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway ◽  
Induced Apoptosis

scholarly journals Neochamaejasmin A Induces Mitochondrial-Mediated Apoptosis in Human Hepatoma Cells via ROS-Dependent Activation of the ERK1/2/JNK Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yangfang Ding ◽  
Qi Xie ◽  
Wenjing Liu ◽  
Zhaohai Pan ◽  
Xinmei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Hepg2 Cells ◽  
Morphological Changes ◽  
Control Group ◽  
Dependent Manner ◽  
Human Hepatoma ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

The botanical constituents of Stellera chamaejasme Linn. exhibit various pharmacological and medicinal activities. Neochamaejasmin A (NCA), one main active constituent of S. chamaejasme, inhibits cell proliferation and induces cell apoptosis in several types of tumor cells. However, the antitumor effect of NCA on hepatocellular carcinoma cells is still unclear. In this study, NCA (36.9, 73.7, and 147.5 μM) significantly inhibited hepatoblastoma-derived HepG2 cell proliferation in a concentration-dependent manner. Hoechst 33258 staining and flow cytometry showed that apoptotic morphological changes were observed and the apoptotic rate was significantly increased in NCA-treated HepG2 cells, respectively. Additionally, the levels of Bax, cleaved caspase-3, and cytoplasmic cytochrome c were increased, while the level of Bcl-2 was decreased in NCA-treated HepG2 cells when compared with the control group. Moreover, we found that the reactive oxygen species (ROS) level was significantly higher and the mitochondrial membrane potential was remarkably lower in NCA-treated HepG2 cells than in the control group. Further studies demonstrated that the levels of p-JNK and p-ERK1/2 were significantly upregulated in NCA-treated HepG2 cells, and pretreatment with JNK and ERK1/2 inhibitors, SP600125 and PD0325901, respectively, suppressed NCA-induced cell apoptosis of HepG2 cells. In addition, NCA also significantly inhibited human hepatoma BEL-7402 cell proliferation and induced cell apoptosis through the ROS-mediated mitochondrial apoptotic pathway. These results implied that NCA induced mitochondrial-mediated cell apoptosis via ROS-dependent activation of the ERK1/2/JNK signaling pathway in HepG2 cells.

Neohesperidin Induces Cell Cycle Arrest, Apoptosis, and Autophagy via the ROS/JNK Signaling Pathway in Human Osteosarcoma Cells

2021 ◽  
pp. 1-24
Author(s):  
Shubin Wang ◽  
Zongguang Li ◽  
Wei Liu ◽  
Guojun Wei ◽  
Naichun Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Signaling Pathway ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Jnk Signaling ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Jnk Signaling Pathway ◽  
Induced Apoptosis

Neohesperidin has anti-oxidative and anti-inflammatory properties and exerts extensive therapeutic effects on various cancers. In this study, the osteosarcoma cell lines were exposed to different concentrations of neohesperidin. Cell proliferation and viability were assessed by CCK-8 and colony-formation assays. The role of neohesperidin in cell cycle progression and apoptosis were analyzed by flow cytometry and western blotting. To identify autophagosomes and autolysosomes, we used a tandem GFP-mRFP-LC3B lentiviral construct. In addition, autophagy was evaluated by examining autophagosome formation using transmission electron microscopy. Intracellular reactive oxygen species (ROS) production was detected by fluorescence microscopy and flow cytometry. Subsequently, the activation of the ROS/JNK signaling pathway was investigated. Neohesperidin could inhibit proliferation and induce apoptosis in SJSA and HOS cells. The formation of autophagosomes indicated that autophagy occurred in neohesperidin-treated cells and the apoptotic effect of neohesperidin was significantly increased after the use of autophagy inhibitors. Subsequently, we found that neohesperidin-induced apoptosis and autophagy were related to the increase in ROS generation and were significantly inhibited by GSH. Moreover, neohesperidin induced activation of the c-Jun N-terminal kinase (JNK) signaling pathway and inhibition of JNK with SP600125 attenuated neohesperidin-induced apoptosis and autophagy simultaneously. Our data indicated that neohesperidin caused G2/M phase arrest and induced apoptosis and autophagy by activating the ROS/JNK pathway in human osteosarcoma cells, suggesting that neohesperidin is a potential drug candidate for the treatment of osteosarcomas.

scholarly journals Huaier Aqueous Extract Induces Hepatocellular Carcinoma Cells Arrest in S Phase via JNK Signaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Chengshuo Zhang ◽  
Jialin Zhang ◽  
Xin Li ◽  
Ning Sun ◽  
Rui Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cyclin D1 ◽  
Signaling Pathway ◽  
Aqueous Extract ◽  
Cell Apoptosis ◽  
S Phase ◽  
Carcinoma Cells ◽  
Jnk Signaling ◽  
Hepatocellular Carcinoma Cells ◽  
Jnk Signaling Pathway

Huaier aqueous extract, the main active constituent of Huaier proteoglycan, has antihepatocarcinoma activity in experimental and clinical settings. However, the potential and associated antihepatoma mechanisms of Huaier extract are not yet fully understood. Therefore, in this study, we aimed to elucidate the inhibitory proliferation effect of Huaier extract on apoptosis and cycle of HepG2 and Bel-7402 cells. Our data demonstrated that incubation with Huaier extract resulted in a marked decrease in cell viability dose-dependently. Flow cytometric analysis showed that a 48 h treatment of Huaier extract caused cell apoptosis. Typical apoptotic nucleus alterations were observed with fluorescence microscope after Hoechst staining. Immunoblot analysis further demonstrated that Huaier extract activated caspase 3 and PARP. Additionally, Huaier extract inhibited the activity of p-ERK, p-p38, and p-JNK in terms of MAPK. Furthermore, Huaier extract induced HCC cells arrest in S phase and decreased the cycle related protein expression ofβ-catenin and cyclin D1. Studies with JNK specific inhibitor, SP600125, showed that Huaier extract induced S phase arrest and decreasedβ-catenin and cyclin D1 expression via JNK signaling pathway. In conclusion, we verify that Huaier extract causes cell apoptosis and induces hepatocellular carcinoma cells arrest in S phase via JNK pathway, which advances our understanding on the molecular mechanisms of Huaier extract in hepatocarcinoma management.

scholarly journals miR-20b-5p attenuates hypoxia-induced apoptosis in cardiomyocytes via the HIF-1α/NF-κB pathway

2020 ◽  
Vol 52 (9) ◽  
pp. 927-934 ◽  
Author(s):  
Zhongquan Zhou ◽  
Songwen Chen ◽  
Zhiming Tian ◽  
Shibing Deng ◽  
Xuying Yi ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Target Genes ◽  
Annexin V ◽  
Pcr Analysis ◽  
H9c2 Cell ◽  
H9c2 Cells ◽  
Flow Cytometry Analysis ◽  
Low Oxygen

Abstract Chronic hypoxia is a common inducer of end-stage cardiovascular disease. In cells under hypoxia, the hypoxia-inducible factor-1 (HIF-1) plays a vital role in regulating downstream target genes. However, the mechanism of hypoxia in cardiomyocytes is still unclear. In this study, we aimed to identify novel downstream epigenetic targets of HIF-1α in cardiomyocytes under hypoxia. H9c2 cells were exposed to hypoxia condition, and quantitative real-time PCR analysis was performed to evaluate the expression of miR-20b-5p. The results indicated that the expression of miR-20b-5p was down-regulated in H9c2 cells under low oxygen condition. Meanwhile, HIF-1α overexpression further down-regulated the miR-20b-5p expression in H9c2 cells transfected with HIF-1α plasmids. In addition, Annexin-V-FITC/PI flow cytometry analysis suggested that overexpression of miR-20b-5p attenuated cell apoptosis under hypoxia condition in H9c2 cells. Western blot analysis showed that the hypoxia apparently increased Bax and cleaved-caspase-3, but decreased Bcl-2 expression in H9c2 cells, indicating that hypoxia-induced NF-κB signaling pathway activation is mediated by miR-20b-5p. Hypoxia-induced H9c2 cell apoptosis was reduced after HIF-1α knockdown as shown by the flow cytometry analysis. In conclusion, we identified that miR-20b-5p plays an important role in mediating cardiomyocytes apoptosis under hypoxia, which is mediated by the HIF-1/NF-κB signaling pathway.

The role of the stress-activated protein kinase (SAPK/JNK) signaling pathway in radiation-induced apoptosis

1998 ◽  
Vol 47 (3) ◽  
pp. 225-232 ◽  
Author(s):  
Marcel Verheij ◽  
Gerald A Ruiter ◽  
Shuraila F Zerp ◽  
Wim J van Blitterswijk ◽  
Zvi Fuks ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Jnk Signaling ◽  
Radiation Induced ◽  
Jnk Signaling Pathway ◽  
Induced Apoptosis

Alkyl-lysophospholipids activate the SAPK/JNK signaling pathway and enhance radiation-induced apoptosis

1999 ◽  
Vol 35 ◽  
pp. S179 ◽  
Author(s):  
G.A. Ruiter ◽  
S.F. Zerp ◽  
H. Bartelink ◽  
W.J. van Blitterswijk ◽  
M. Verheij
Keyword(s):  
Signaling Pathway ◽  
Jnk Signaling ◽  
Radiation Induced ◽  
Jnk Signaling Pathway ◽  
Induced Apoptosis

Effect of pharmacologic inhibition of c-Jun N-terminal kinase (JNK) signaling pathway on cell proliferation and cell cycle progression in human granulosa cell tumor.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22004-e22004
Author(s):  
Ozgur Oktem ◽  
Meltem Muftuoglu ◽  
Filiz Senbabaoglu ◽  
Bulent Urman
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Granulosa Cell ◽  
Dependent Manner ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Curative Therapy ◽  
Jnk Signaling Pathway ◽  
Dose Dependent

e22004 Background: No data are available regarding the signaling pathways that controls the proliferation of granulosa cell tumors (GCT). Preliminary findings showing the activation of c-Jun N-terminal kinase (JNK) signaling pathway in the proliferating granulosa cells has led us to investigate the role of this pathway in human GCT. Methods: Human GCT line COV 434 was used. Cell proliferation was monitored real-time quantitatively for 120h using an impedance-based system. Two different pharmacologic JNK inhibitors SP600125 and AS601245 were used. Their inhibitory concentrations were determined in western blot. Cell cycle was analyzed with flow cytometry and apoptosis with yo-pro-1 staining. Results: First, the growth characteristics of this cell line was delineated (Table 1A). Then the cells were treated with the inhibitors at the indicated doses during the log phase. Their proliferation was significantly halted in a dose-dependent manner by both inhibitors (Table 1B). Furthermore, the cells failed to complete mitosis, and began to accumulate at G2 in a dose dependent manner when JNK pathway was interrupted with AS601245 (59%) and SP600125 (39%) during G2/M transition compared to control cells (7%) proceeding through G2/M phase regularly (p<0.001). Compared to 3.5% of control cells, 14% and 30% of the cells underwent apoptosis when treated with 50 µM SP600125 and AS601245, respectively. At 100 µM, the apoptotic fraction increased to 68% and 76%, respectively (p<0.01). Conclusions: These results suggest that pharmacologic manipulation of JNK pathway may provide a therapeutic benefit in the treatment of GCT for which currently, no curative therapy exists beyond surgery. Funded by a Grant to Ozgur Oktem (TUBITAK109S164). [Table: see text]

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