Role of Apoptosis in disease

Favaloro, Bartolo; Allocati, Nerino; Graziano, Vincenzo; Ilio, Carmine Di; Laurenzi, Vincenzo De

doi:10.18632/aging.100459

Cited by 483 publications

(376 citation statements)

References 183 publications

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“…In this case, signaling cascade is mainly initiated by caspase-8 cleavage. Both apoptotic mechanisms converge in the induction of caspases-3/7 [26].…”

Section: 4mentioning

confidence: 99%

Edelfosine lipid nanosystems overcome drug resistance in leukemic cell lines

et al. 2013

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Although current therapies have improved leukemia survival rates, adverse drug effects and relapse are frequent. Encapsulation of edelfosine (ET) in lipid nanoparticles (LN) improves its oral bioavailability and decreases its toxicity. Here we evaluated the efficacy of ET-LN in myeloid leukemia cell lines. Drug-loaded LN were as effective as free ET in sensitive leukemia cell lines. Moreover, the encapsulated drug overcame the resistance of the K562 cell line to the drug. LN containing ET might be used as a promising drug delivery system in leukemia due to their capacity to overcome the in vivo pitfalls of the free drug and their efficacy in vitro in leukemia cell lines.

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“…In this case, signaling cascade is mainly initiated by caspase-8 cleavage. Both apoptotic mechanisms converge in the induction of caspases-3/7 [26].…”

Section: 4mentioning

confidence: 99%

Edelfosine lipid nanosystems overcome drug resistance in leukemic cell lines

et al. 2013

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“…The control or any disorder in it has the effective role in malignant deformation process, cancer progress and metastases (Bold et al, 1997;Kamesaki et al, 1998). Apoptosis is done through two different pathways including the death-receptor pathway and mitochondrial pathway (Favaloro al., 2012). The B-cell lymphoma 2 (Bcl-2) family represents apoptosis regulating proteins integrating diverse intra-and extracellularly generated survival and death signals.…”

Section: Introductionmentioning

confidence: 99%

Low Expression of the bcl2 Gene in Gastric Adenocarcinomas in Mazandaran Province of Iran

Mirmajidi¹,

Ataee²,

Barzegar³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Gastric cancer accounts for about 8% of the total cancer cases and 10% of total cancer deaths worldwide. It is the second lethal cancer after esophageal cancer and is considered the fourth most common cancer in north and northwest Iran. The bcl2 family has a key role in the regulation of apoptosis and change in its expression can contribute to cancer. This study initially scheduled to determine the expression of bcl2 gene in tissue samples of adenocarcinoma cancer patients. Materials and Methods: A total of 10 samples of gastric adenocarcinoma and 10 of normal tissues from Sari hospital were selected and after DNA extraction from tissues, bcl2 gene expression assayed by real-time PCR. Results: Our results demonstrated higher expression of the bcl2 gene in control compared with cancer and marginal cancer tissues. Conclusions: On one hand BCL2 plays an important role as an oncogene to inhibit apoptosis; on the other hand, it can initiate cell cycle arrest at G0 stage. Our observed association between its expression and patient survival is quite conflicting and may be tissue-specific. The data suggest expression both tumoural and non-tumoral(marginal) groups have lowered expression than controls (P>0.05). Due to the low number of samples we could not examine the relationship with clinicopathological features. However, bcl-2 expression may be important for prognostic outcome or a useful target for therapeutic intervention.

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“…However, in various human disease states, including neurodegeneration, autoimmunity, and cancer, a deregulation or malfunction of this inherent program occurs and cells may develop resistance to apoptosis. 5,6 Apoptosis occurs through two main signaling pathways: an extrinsic pathway that utilizes a diversified group of cell surface death receptors; [7][8][9][10][11][12][13][14] and an intrinsic pathway that utilizes various intracellular organelles to execute the programmed cell death machinery. [15][16][17][18][19][20] An important and well-studied point of control for both the extrinsic and intrinsic apoptotic pathways is the Bcl-2 family of proteins that comprise both pro-and antiapoptotic members and regulate the apoptotic program through a tightly controlled series of checks and balances.…”

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confidence: 99%

T-cell development of resistance to apoptosis is driven by a metabolic shift in carbon source and altered activation of death pathways

et al. 2015

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We developed a model system to investigate apoptotic resistance in T cells using osmotic stress (OS) to drive selection of deathresistant cells. Exposure of S49 (Neo) T cells to multiple rounds of OS followed by recovery of surviving cells resulted in the selection of a population of T cells (S49 ) that failed to die in response to a variety of intrinsic apoptotic stimuli including acute OS, but remained sensitive to extrinsic apoptotic initiators. Genome-wide microarray analysis comparing the S49 (OS 4-25) with the parent S49 (Neo) cells revealed over 8500 differentially regulated genes, with almost 90% of those identified being repressed. Surprisingly, our data revealed that apoptotic resistance is not associated with expected changes in pro-or antiapoptotic Bcl-2 family member genes. Rather, these cells lack several characteristics associated with the initial signaling or activation of the intrinsic apoptosis pathway, including failure to increase mitochondrial-derived reactive oxygen species, failure to increase intracellular calcium, failure to deplete glutathione, failure to release cytochrome c from the mitochondria, along with a lack of induced caspase activity. The S49 (OS 4-25) cells exhibit metabolic characteristics indicative of the Warburg effect, and, despite numerous changes in mitochondria gene expression, the mitochondria have a normal metabolic capacity. Interestingly, the S49 (OS 4-25) cells have developed a complete dependence on glucose for survival, and glucose withdrawal results in cell death with many of the essential characteristics of apoptosis. Furthermore, we show that other dietary sugars such as galactose support the viability of the S49 (OS 4-25) cells in the absence of glucose; however, this carbon source sensitizes these cells to die. Our findings suggest that carbon substrate reprogramming for energy production in the S49 (OS 4-25) cells results in stimulusspecific recognition defects in the activation of intrinsic apoptotic pathways.

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Role of Apoptosis in disease

Cited by 483 publications

References 183 publications

Edelfosine lipid nanosystems overcome drug resistance in leukemic cell lines

Edelfosine lipid nanosystems overcome drug resistance in leukemic cell lines

Low Expression of the bcl2 Gene in Gastric Adenocarcinomas in Mazandaran Province of Iran

T-cell development of resistance to apoptosis is driven by a metabolic shift in carbon source and altered activation of death pathways

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