scholarly journals Chloroquine synergizes with FTS to enhance cell growth inhibition and cell death

Oncotarget ◽  
2013 ◽  
Vol 5 (1) ◽  
pp. 173-184 ◽  
Author(s):  
Eran Schmukler ◽  
Eya Wolfson ◽  
Roni Haklai ◽  
Galit Elad-Sfadia ◽  
Yoel Kloog ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cell Growth Inhibition ◽  
Enhance Cell Growth

Mitogen-activated protein kinase inhibitors differently affect the growth inhibition and death of a proteasome inhibitor, MG132-treated human pulmonary fibroblast cells

2011 ◽  
Vol 30 (12) ◽  
pp. 1945-1954 ◽  
Author(s):  
Woo Hyun Park
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Proteasome Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Cell Growth Inhibition ◽  
P38 Inhibitor ◽  
Mitogen Activated Protein ◽  
Mapk Inhibitors ◽  
Pulmonary Fibroblast

Carbobenzoxy-Leu-Leu-leucinal (MG132) as a proteasome inhibitor can induce growth inhibition and death in lung cancer or normal cells. However, little is known about relationship between proteasome inhibition and mitogen-activated protein kinase (MAPK) signaling in normal lung cells. Thus, in the present study, we investigated the effects of MAPK inhibitors on MG132-treated human pulmonary fibroblast (HPF) cells in relation to cell growth inhibition, cell death, reactive oxygen species (ROS) and glutathione (GSH). Treatment with 15 μM MG132 increased ROS levels including mitochondrial O2•− and GSH depleted cell numbers in HPF cells at 24 hours. MAP kinase or ERK kinase (MEK) inhibitor did not significantly affect cell growth inhibition, cell death, the loss of mitochondrial membrane potential (MMP; Δ Ψm), ROS level and GSH depletion in MG132-treated HPF cells. c-Jun N-terminal kinase (JNK) inhibitor attenuated the growth inhibition and death by MG132. This inhibitor also significantly decreased O2•− level in MG132-treated HPF cells. Although p38 inhibitor slightly enhanced HPF cell growth inhibition by MG132, this inhibitor and siRNA prevented HPF cell death induced by MG132. p38 inhibitor also attenuated d O2•− level and GSH depletion. Moreover, extracellular signal regulated kinase (ERK), JNK or p38 siRNA did not strongly affect ROS levels in MG132-treated HPF cells. ERK and JNK siRNAs decreased anonymous ubiquitinated protein levels in MG132-treated HPF cells. In conclusion, MAPK inhibitors differently affected the growth inhibition and death of MG132-treated HPF cells. Especially, p38 inhibitor attenuated HPF cell death by MG132, which was in part related to changes in ROS and GSH levels.

scholarly journals Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death

2010 ◽  
Vol 67 (5) ◽  
pp. 1167-1178 ◽  
Author(s):  
Bettina M. Kaminski ◽  
Andreas Weigert ◽  
Bernhard Brüne ◽  
Marco Schumacher ◽  
Uwe Wenzel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Growth Inhibition ◽  
Colorectal Cancer Cells

scholarly journals Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e75269 ◽  
Author(s):  
Sari Schokoroy ◽  
Dolly Juster ◽  
Yoel Kloog ◽  
Ronit Pinkas-Kramarski
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cell Growth Inhibition

scholarly journals MnTE-2-PyP Suppresses Prostate Cancer Cell Growth via H2O2 Production

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 490
Author(s):  
Yuxiang Zhu ◽  
Elizabeth A. Kosmacek ◽  
Arpita Chatterjee ◽  
Rebecca E. Oberley-Deegan
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cell Cycle Progression ◽  
Cell Growth Inhibition ◽  
Lncap Cells ◽  
Cycle Progression ◽  
Pc3 Cells

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, a superoxide dismutase (SOD) mimic, is a known radioprotector of normal tissues. Our recent work demonstrated that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this study, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting the growth of PC3 and LNCaP cells, but the increased H2O2 levels affected the two cancer cells differently. In PC3 cells, many proteins were thiol oxidized with MnTE-2-PyP treatment, including Ser/Thr protein phosphatase 1 beta catalytic subunit (PP1CB). This resulted in reduced PP1CB activity; however, overall cell cycle progression was not altered, so this is not the main mechanism of PC3 cell growth inhibition. High H2O2 levels by MnTE-2-PyP treatment induced nuclear fragmentation, which could be synergistically enhanced with radiotherapy. In LNCaP cells, thiol oxidation by MnTE-2-PyP treatment was not observed previously and, similarly to PC3 cells, there was no effect of MnTE-2-PyP treatment on cell cycle progression. However, in LNCaP cells, MnTE-2-PyP caused an increase in low RNA population and sub-G1 population of cells, which indicates that MnTE-2-PyP treatment may cause cellular quiescence or direct cancer cell death. The protein oxidative modifications and mitotic catastrophes caused by MnTE-2-PyP may be the major contributors to cell growth inhibition in PC3 cells, while in LNCaP cells, tumor cell quiescence or cell death appears to be major factors in MnTE-2-PyP-induced growth inhibition.

scholarly journals PSF Knockdown Enhances Apoptosis via Downregulation of LC3B in Human Colon Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Tamotsu Tsukahara ◽  
Yoshikazu Matsuda ◽  
Hisao Haniu
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Physiological Role ◽  
Colon Cancer Cells ◽  
Cell Growth Inhibition ◽  
Ht 29

Our previous study demonstrated that PTB-associated splicing factor (PSF) is an important regulator of cell death and plays critical roles in the survival and growth of colon cancer cells. However, the molecular mechanism that activates these downstream signaling events remains unknown. To address this issue, we investigated the effects of PSF knockdown in two different colon cancer cell lines, DLD-1 and HT-29. We found that knockdown of PSF markedly decreased the autophagic molecule LC3B in DLD-1 cells but not in HT-29 cells. Furthermore, DLD-1 cells were more susceptible to PSF knockdown-induced cell growth inhibition and apoptosis than HT-29 cells. This susceptibility is probably a result of LC3B inhibition, given the known relationship between autophagy and apoptosis. C3B is associated with a number of physiological processes, including cell growth and apoptotic cell death. Our results suggest that autophagy is inhibited by PSF knockdown and that apoptosis and cell growth inhibition may act together to mediate the PSF-LC3B signaling pathway. Furthermore, we found that the peroxisome proliferator-activated receptor gamma (PPARγ)-PSF complex induced LC3B downregulation in DLD-1 cells. The results of this study identify a new physiological role for the PSF-LC3B axis as a potential endogenous modulator of colon cancer treatment.

Tetra-O-Methyl Nordihydroguaiaretic Acid Inhibits Growth and Induces Death of Leukemia Cells Independent of Cdc2 and Survivin.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4366-4366
Author(s):  
Bing Z. Carter ◽  
Duncan H. Mak ◽  
Wendy D. Schober ◽  
Jonathan Heller ◽  
Michael Andreeff
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Survivin Expression ◽  
Leukemic Cell ◽  
Nordihydroguaiaretic Acid ◽  
Leukemia Cells ◽  
Cell Growth Inhibition ◽  
G2 Arrest ◽  
Leukemic Cell Lines

Abstract Tetra-O-methyl nordihydroguaiaretic acid (M4N) was shown to induce G2 arrest in mammalian cells and suppress the growth of human xenograft tumors by inhibiting Cdc2 and survivin expression. We have previously shown that inhibition of survivin expression by antisense oligonucleotide induced G2 block and subsequent cell death in HL-60 cells. In this study, we examined the effect of M4N on leukemic cells and found that M4N inhibited growth and induced apoptosis in various leukemic cell lines and blasts from AML patients at concentrations from 5μM to 40μM. However, Cdc2 and survivin levels were not significantly affected. In agreement with these results, no G2 arrest was observed. Cell death and cell growth inhibition induced by M4N in leukemia cells were dependent neither on XIAP, Bcl-2, or Bcl-XL levels nor on caspase-8. Although M4N induced the loss of mitochondrial membrane potential in HL-60 cells, overexpression of Bcl-2 or Bcl-XL did not attenuate cell growth inhibition and cell death induced by M4N. M4N did not promote cell differentiation in HL-60 cells. Interestingly, significant inhibition of AKT and to a lesser degree of ERK phosphorylation was observed at 24 hours in OCI-AML3 cells treated with M4N. Collectively, our data showed that M4N inhibited cell growth and induced cell death in both leukemic cell lines and AML patient sample through a mechanism not mediated by Cdc2 and survivin inhibition and independent of death receptor and mitochondrial apoptotic pathways.

Jab1-siRNA Induces Cell Growth Inhibition and Cell Cycle Arrest in Gall Bladder Cancer Cells via Targeting Jab1 Signalosome

2020 ◽  
Vol 19 (16) ◽  
pp. 2019-2033 ◽  
Author(s):  
Pratibha Pandey ◽  
Mohammad H. Siddiqui ◽  
Anu Behari ◽  
Vinay K. Kapoor ◽  
Kumudesh Mishra ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Cell Growth ◽  
Gall Bladder ◽  
Growth Inhibition ◽  
Cell Cycle Arrest ◽  
Gall Bladder Cancer ◽  
Cell Growth Inhibition ◽  
Cycle Arrest ◽  
Apoptotic Induction

Background: The aberrant alteration in Jab1 signalosome (COP9 Signalosome Complex Subunit 5) has been proven to be associated with the progression of several carcinomas. However the specific role and mechanism of action of Jab1 signalosome in carcinogenesis of gall bladder cancer (GBC) are poorly understood. Objective: The main objective of our study was to elucidate the role and mechanism of Jab1 signalosome in gall bladder cancer by employing siRNA. Methods: Jab1 overexpression was identified in gall bladder cancer tissue sample. The role of Jab1-siRNA approach in cell growth inhibition and apoptotic induction was then examined by RT-PCR, Western Blotting, MTT, ROS, Hoechst and FITC/Annexin-V staining. Results: In the current study, we have shown that overexpression of Jab1 stimulated the proliferation of GBC cells; whereas downregulation of Jab1 by using Jab1-siRNA approach resulted incell growth inhibition and apoptotic induction. Furthermore, we found that downregulation of Jab1 induces cell cycle arrest at G1 phase and upregulated the expression of p27, p53 and Bax gene. Moreover, Jab1-siRNA induces apoptosis by enhancing ROS generation and caspase-3 activation. In addition, combined treatment with Jab1-siRNA and gemicitabine demonstrated an enhanced decline in cell proliferation which further suggested increased efficacy of gemcitabine at a very lower dose (5μM) in combination with Jab1-siRNA. Conclusion: In conclusion, our study strongly suggests that targeting Jab1 signalosome could be a promising therapeutic target for the treatment of gall bladder cancer.

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