Abstract 3887: Reversible inhibition of CDK4/CDK6 sensitizes hematological tumor cells for cytotoxic killing by inducing sequential G1 arrest and synchronous S phase entry that enhances the intrinsic apoptosis pathway

Background/Aim. Apoptotic Protease Activating Factor-1 (Apaf-1) is a key molecule in the intrinsic or mitochondrial pathway of apoptosis. Some pathological conditions such as cancer, stroke, and neurodegenerative diseases, are the result of disregulation in the intrinsic apoptosis pathway. The aim of this study was to analyse the immunohistochemical expression of Apaf-1 in ACC tumor cells of the salivary glands and its correlation with clinicopathological parameters (gender, age, localization, histological type and overall survival). Methods. Formalin-fixed, paraffin-embedded tissues from 50 human ACC of the salivary glands, male and female, average age 58 years, were used for our present study. We used the technique of tissue microarray (TMA blocks). Sections from the TMA mould, 5?m thick, were stained with the streptavidin-biotin immunohistochemical technique using primary antibodies specific for Apaf-1 (Leica Biosystems, Newcastle, UK). Stained tissue sections were analyzed by the light microscope (Olympus type BH-2). Based on the data collected, the database was created in SPSS software v. 22.0 (SPSS Inc., Chicago, ILL, USA), which was used for a further statistical analysis. The statistical data analysis included methods of descriptive and analytical (inferential) statistics. Results. The results of the immunohistochemical analysis of Apaf-1 expression in the samples of patients with ACC of the salivary glands were compared with the clinicopathological parameters of these patients. The immunohistochemical expression of Apaf-1 showed no statistical significance with regard to the patients gender (p=0.552), age (p=0.106), histological tumor type (p=0.654) and localization of ACC in the salivary glands (p=0.486). There was no statistically significant correlation observed between overall survival of ACC patients and Apaf-1 expression in tumor cells (p=0.340,Long-Rank test). Conclusion. With regard to ACC, Apaf-1 expression is not in correlation with clinicopathological parameters (gender, age, localization, histological tumor type, outcome of the disease, and overall survival). Therefore, we believe Apaf-1 cannot be regarded as an independent prognostic factor.

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Scutellarein selectively targets multiple myeloma cells by increasing mitochondrial superoxide production and activating intrinsic apoptosis pathway

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2018.09.024 ◽

2019 ◽

Vol 109 ◽

pp. 2109-2118 ◽

Cited By ~ 3

Author(s):

Lin Shi ◽

Yi Wu ◽

Dian liang LV ◽

Lei Feng

Keyword(s):

Multiple Myeloma ◽

Superoxide Production ◽

Intrinsic Apoptosis ◽

Apoptosis Pathway ◽

Myeloma Cells ◽

Mitochondrial Superoxide ◽

Intrinsic Apoptosis Pathway

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Amphiregulin Regulates Phagocytosis-Induced Cell Death in Monocytes via EGFR and the Bcl-2 Protein Family

Mediators of Inflammation ◽

10.1155/2019/1603131 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Christopher Platen ◽

Stephan Dreschers ◽

Jessica Wappler ◽

Andreas Ludwig ◽

Stefan Düsterhöft ◽

...

Keyword(s):

Cell Death ◽

Bacterial Infections ◽

Caspase 3 ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Dependent Manner ◽

Intrinsic Apoptosis ◽

Caspase 9 ◽

Apoptosis Pathway ◽

Intrinsic Apoptosis Pathway

Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphiregulin (AREG) is increasingly expressed on the cell surface of neonatal monocytes, resulting in remarkably higher soluble AREG levels after proteolytic shedding. In this study, we found that E. coli-infected neonatal monocytes show an increased phosphorylation of ERK, increased expression of Bcl-2 and Bcl-XL, and reduced levels of cleaved caspase-3 and caspase-9 compared to adult monocytes. In both cell types, additional stimulation with soluble AREG further increased ERK activation and expression of Bcl-2 and Bcl-XL and reduced levels of cleaved caspase-3 and caspase-9 in an EGFR-dependent manner. These data suggest that reduced PICD of neonatal monocytes could be due to reduced intrinsic apoptosis and that AREG can promote protection against PICD. This reduction of the intrinsic apoptosis pathway in neonatal monocytes could be relevant for severely prolonged inflammatory responses of neonates.

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Alantolactone induces apoptosis in THP‐1 cells through STAT3, survivin inhibition, and intrinsic apoptosis pathway

Chemical Biology & Drug Design ◽

10.1111/cbdd.13778 ◽

2020 ◽

Author(s):

Bashir Ahmad ◽

Yaser Gamallat ◽

Pengyu Su ◽

Akbar Husain ◽

Ata Ur Rehman ◽

...

Keyword(s):

Intrinsic Apoptosis ◽

Apoptosis Pathway ◽

Intrinsic Apoptosis Pathway

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Cell death following the loss of ADAR1 mediated A-to-I RNA editing is not effected by the intrinsic apoptosis pathway

Cell Death and Disease ◽

10.1038/s41419-019-2160-6 ◽

2019 ◽

Vol 10 (12) ◽

Cited By ~ 4

Author(s):

Carl R. Walkley ◽

Benjamin T. Kile

Keyword(s):

Cell Death ◽

Rna Editing ◽

Rna Structure ◽

Fetal Liver ◽

Loss Of Function ◽

Intrinsic Apoptosis ◽

Triple Mutant ◽

Apoptosis Pathway ◽

Mitochondrial Apoptosis Pathway ◽

Intrinsic Apoptosis Pathway

AbstractModifications of RNA, collectively termed as the epitranscriptome, are widespread, evolutionarily conserved and contribute to gene regulation and protein diversity in healthy and disease states. There are >160 RNA modifications described, greatly exceeding the number of modifications to DNA. Of these, adenosine-to-inosine (A-to-I) RNA editing is one of the most common. There are tens of thousands of A-to-I editing sites in mouse, and millions in humans. Upon translation or sequencing an inosine base is decoded as guanosine, leading to A-to-G mismatches between the RNA and DNA. Inosine has different base pairing properties to adenosine and as a result editing not only alters the RNA code but can also change the RNA structure. In mammals A-to-I editing is performed by ADAR1 and ADAR2. A feature of murine loss of function ADAR1 alleles is cell death and a failure to survive embryogenesis. Adar1−/− and editing deficient (Adar1E861A/E861A) mice die between E11.75–13.5 of failed hematopoiesis. Strikingly this phenotype is rescued by the deletion of the cytosolic dsRNA sensor MDA5 or its downstream adaptor MAVS, a mechanism conserved in human and mouse. Current literature indicates that the loss of ADAR1 leads to cell death via apoptosis, yet this has not been genetically established. We report that blockade of the intrinsic (mitochondrial) apoptosis pathway, through the loss of both BAK and BAX, does not rescue or modify the cellular phenotype of the fetal liver or extend the lifespan of ADAR1 editing deficient embryos. We had anticipated that the loss of BAK and BAX would rescue, or at least significantly extend, the gestational viability of Adar1E861A/E861A embryos. However, the triple mutant Adar1E861A/E861ABak−/−Bax−/− embryos that were recovered at E13.5 were indistinguishable from the Adar1E861A/E861A embryos with BAK and BAX. The results indicate that cell death processes not requiring the intrinsic apoptosis pathway are triggered by MDA5 following the loss of ADAR1.

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