scholarly journals Redox Regulation of STAT1 and STAT3 Signaling

2020 ◽  
Vol 21 (19) ◽  
pp. 7034
Author(s):  
Elena Butturini ◽  
Alessandra Carcereri de Prati ◽  
Sofia Mariotto
Keyword(s):  
Cell Cycle ◽  
Immune Response ◽  
Cell Death ◽  
Redox Regulation ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Post Translational Modifications ◽  
Environmental Signals ◽  
Stat3 Signaling

STAT1 and STAT3 are nuclear transcription factors that regulate genes involved in cell cycle, cell survival and immune response. The cross-talk between these signaling pathways determines how cells integrate the environmental signals received ultimately translating them in transcriptional regulation of specific sets of genes. Despite being activated downstream of common cytokine and growth factors, STAT1 and STAT3 play essentially antagonistic roles and the disruption of their balance directs cells from survival to apoptotic cell death or from inflammatory to anti-inflammatory responses. Different mechanisms are proposed to explain this yin-yang relationship. Considering the redox aspect of STATs proteins, this review attempts to summarize the current knowledge of redox regulation of STAT1 and STAT3 signaling focusing the attention on the post-translational modifications that affect their activity.

scholarly journals Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Viktorija Juric ◽  
Lance Hudson ◽  
Joanna Fay ◽  
Cathy E. Richards ◽  
Hanne Jahns ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Cortical Neurons ◽  
Apoptotic Cell ◽  
Cdk Inhibitors ◽  
Induce Cell Death ◽  
Viability Loss ◽  
Cycle Arrest ◽  
Recurrent Gbm

AbstractActivation of cyclin-dependent kinases (CDKs) contributes to the uncontrolled proliferation of tumour cells. Genomic alterations that lead to the constitutive activation or overexpression of CDKs can support tumourigenesis including glioblastoma (GBM), the most common and aggressive primary brain tumour in adults. The incurability of GBM highlights the need to discover novel and more effective treatment options. Since CDKs 2, 7 and 9 were found to be overexpressed in GBM, we tested the therapeutic efficacy of two CDK inhibitors (CKIs) (CYC065 and THZ1) in a heterogeneous panel of GBM patient-derived cell lines (PDCLs) cultured as gliomaspheres, as preclinically relevant models. CYC065 and THZ1 treatments suppressed invasion and induced viability loss in the majority of gliomaspheres, irrespective of the mutational background of the GBM cases, but spared primary cortical neurons. Viability loss arose from G2/M cell cycle arrest following treatment and subsequent induction of apoptotic cell death. Treatment efficacies and treatment durations required to induce cell death were associated with proliferation velocities, and apoptosis induction correlated with complete abolishment of Mcl-1 expression, a cell cycle-regulated antiapoptotic Bcl-2 family member. GBM models generally appeared highly dependent on Mcl-1 expression for cell survival, as demonstrated by pharmacological Mcl-1 inhibition or depletion of Mcl-1 expression. Further analyses identified CKI-induced Mcl-1 loss as a prerequisite to establish conditions at which the BH3-only protein Bim can efficiently induce apoptosis, with cellular Bim amounts strongly correlating with treatment efficacy. CKIs reduced proliferation and promoted apoptosis also in chick embryo xenograft models of primary and recurrent GBM. Collectively, these studies highlight the potential of these novel CKIs to suppress growth and induce cell death of patient-derived GBM cultures in vitro and in vivo, warranting further clinical investigation.

scholarly journals Transcriptional network constituted of CBP, Ku70, NOX2, and BAX prevents the cell death of necrosis, paraptosis, and apoptosis in human melanoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Liang Ding ◽  
Yalei Wen ◽  
Xin Zhang ◽  
Fang Zhao ◽  
Kenao Lv ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Apoptotic Cell ◽  
Human Melanoma ◽  
Transcriptional Network ◽  
Multiple Roles ◽  
Creb Binding Protein ◽  
Cycle Arrest ◽  
Intracellular Ros ◽  
High Level

AbstractCREB-binding protein (CBP) is an acetyltransferase known to play multiple roles in the transcriptions of genes involving oxidative metabolism, cell cycle, DNA damage checkpoints, and cell death. In this study, CBP was found to positively regulate the expression of Ku70, and both CBP and Ku70 were found to negatively regulate the expression of NOX2, therefore, mitigating the intracellular ROS in human melanoma. Knocking down CBP or Ku70 induced necrotic and paraptotic cell death as indicated by high-level intracellular ROS, cytoplasmic vacuolization, and cell cycle arrest in the S phase. In addition, chromosomal condensations were also observed in the cells proceeding necrotic and paraptotic cell death, which was found to be related to the BAX-associated intrinsic pathway of apoptotic cell death, when Ku70 was decreased either by CBP depletion or by Ku70 depletion directly. Our results, therefore, supported the idea that CBP, Ku70, BAX, and NOX2 have formed a transcriptional network in the prevention of cell death of necrosis, paraptosis, and apoptosis in human melanoma.

scholarly journals Transcriptome Analysis Reveals HgCl2 Induces Apoptotic Cell Death in Human Lung Carcinoma H1299 Cells through Caspase-3-Independent Pathway

2021 ◽  
Vol 22 (4) ◽  
pp. 2006
Author(s):  
Mi Jin Kim ◽  
Jinhong Park ◽  
Jinho Kim ◽  
Ji-Young Kim ◽  
Mi-Jin An ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Transcriptome Analysis ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Expression Patterns ◽  
Nitrogen Compound ◽  
Apoptotic Cell Death ◽  
Mercury Chloride ◽  
Rna Seq

Mercury is one of the detrimental toxicants that can be found in the environment and exists naturally in different forms; inorganic and organic. Human exposure to inorganic mercury, such as mercury chloride, occurs through air pollution, absorption of food or water, and personal care products. This study aimed to investigate the effect of HgCl2 on cell viability, cell cycle, apoptotic pathway, and alters of the transcriptome profiles in human non-small cell lung cancer cells, H1299. Our data show that HgCl2 treatment causes inhibition of cell growth via cell cycle arrest at G0/G1- and S-phase. In addition, HgCl2 induces apoptotic cell death through the caspase-3-independent pathway. Comprehensive transcriptome analysis using RNA-seq indicated that cellular nitrogen compound metabolic process, cellular metabolism, and translation for biological processes-related gene sets were significantly up- and downregulated by HgCl2 treatment. Interestingly, comparative gene expression patterns by RNA-seq indicated that mitochondrial ribosomal proteins were markedly altered by low-dose of HgCl2 treatment. Altogether, these data show that HgCl2 induces apoptotic cell death through the dysfunction of mitochondria.

scholarly journals The Application of Embelin for Cancer Prevention and Therapy

Molecules ◽  
2018 ◽  
Vol 23 (3) ◽  
pp. 621 ◽  
Author(s):  
Jeong-Hyeon Ko ◽  
Seok-Geun Lee ◽  
Woong Yang ◽  
Jae-Young Um ◽  
Gautam Sethi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Prevention ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Biological Properties ◽  
Multiple Cancer ◽  
Stat3 Signaling ◽  
Oncogenic Pathways ◽  
Cell Death Mechanisms

Embelin is a naturally-occurring benzoquinone compound that has been shown to possess many biological properties relevant to human cancer prevention and treatment, and increasing evidence indicates that embelin may modulate various characteristic hallmarks of tumor cells. This review summarizes the information related to the various oncogenic pathways that mediate embelin-induced cell death in multiple cancer cells. The mechanisms of the action of embelin are numerous, and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and modulate the NF-κB, p53, PI3K/AKT, and STAT3 signaling pathways. Embelin also induces autophagy in cancer cells; however, these autophagic cell-death mechanisms of embelin have been less reported than the apoptotic ones. Recently, several autophagy-inducing agents have been used in the treatment of different human cancers, although they require further exploration before being transferred from the bench to the clinic. Therefore, embelin could be used as a potential agent for cancer therapy.

scholarly journals RUNX Family Participates in the Regulation of p53-Dependent DNA Damage Response

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Toshinori Ozaki ◽  
Akira Nakagawara ◽  
Hiroki Nagase
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Dna Damage Response ◽  
Apoptotic Cell ◽  
Genetic Alterations ◽  
Apoptotic Cell Death ◽  
Cycle Arrest ◽  
Damage Response

A proper DNA damage response (DDR), which monitors and maintains the genomic integrity, has been considered to be a critical barrier against genetic alterations to prevent tumor initiation and progression. The representative tumor suppressor p53 plays an important role in the regulation of DNA damage response. When cells receive DNA damage, p53 is quickly activated and induces cell cycle arrest and/or apoptotic cell death through transactivating its target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death such asp21WAF1,BAX, andPUMA. Accumulating evidence strongly suggests that DNA damage-mediated activation as well as induction of p53 is regulated by posttranslational modifications and also by protein-protein interaction. Loss of p53 activity confers growth advantage and ensures survival in cancer cells by inhibiting apoptotic response required for tumor suppression. RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription factor and is closely involved in a variety of cellular processes including development, differentiation, and/or tumorigenesis. In this review, we describe a background of p53 and a functional collaboration between p53 and RUNX family in response to DNA damage.

scholarly journals Interactions between hydatid cyst and regulated cell death may provide new therapeutic opportunities

Parasite ◽  
2019 ◽  
Vol 26 ◽  
pp. 70 ◽  
Author(s):  
Sirous Mehrani Moghaddam ◽  
Stephane Picot ◽  
Ehsan Ahmadpour
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Current Knowledge ◽  
Cyst Formation ◽  
Response Modulation ◽  
Intermediate Hosts ◽  
New Horizons ◽  
Larval Stages ◽  
Zoonotic Infections ◽  
Regulated Cell Death

Cystic echinococcosis and alveolar echinococcosis are chronic zoonotic infections, transmitted throughout the world. Development of the cestode larval stages in the liver and lungs causes damage to intermediate hosts, including humans. Several pathways leading to the suppression of host immune response and the survival of the cysts in various hosts are known. Immune response modulation and regulated cell death (RCD) play a fundamental role in cyst formation, development and pathogenesis. RCD, referring to apoptosis, necrosis and autophagy, can be triggered either via intrinsic or extrinsic cell stimuli. In this review, we provide a general overview of current knowledge on the process of RCD during echinococcosis. The study of interactions between RCD and Echinococcus spp. metacestodes may provide in-depth understanding of echinococcosis pathogenesis and open new horizons for human intervention and treatment of the disease.

scholarly journals Antiproliferative activities of tricyclic amides derived from β-caryophyllene via the Ritter reaction against MDA-MB-231 breast cancer cells

2020 ◽  
Vol 11 (1) ◽  
pp. 118-124 ◽  
Author(s):  
XiXi Xu ◽  
Ariane Roseblade ◽  
Tristan Rawling ◽  
Alison T. Ung
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Apoptotic Cell ◽  
Ritter Reaction ◽  
Cycle Progression ◽  
The Ritter Reaction ◽  
Antiproliferative Activities

Tricyclic amides were successfully synthesised from β-caryophyllene via the Ritter reaction. Amides 3c and 6b inhibited proliferation of MDA-MB-231 cells. Compound 6b inhibited cell cycle progression and induced predominantly apoptotic cell death.

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