Apoptosis

and, Lyonel G. Israels; Israels, Esther D.

doi:10.1002/stem.170306

Cited by 73 publications

(63 citation statements)

References 31 publications

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“…Injury in MI and stroke occurs in the infarcted area as adjacent cells undergo apoptosis [6]. In this way, cell damage induces p53 expression which in turn regulates the transcription of a number of apoptotic genes.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis during the acute and chronic myocardial infarction has been demonstrated in human and animal studies [3][4][5]. Apoptosis can be induced by DNA damage and p53 up-regulation [6] which is affected by oxidative stress. Oxidative stress due to reactive oxygen species (ROS) takes part in oxygen toxicity causing damage to cellular and subcellular organelles such as the cellular membrane [7,8] and mitochondria [9] or sarcoplasmic reticulum [10] in cardiac myocytes.…”

Section: Introductionmentioning

confidence: 99%

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The role of p53, bax, bcl2, and 8-OHdG in human acute myocardial infarction

et al. 2010

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Apoptosis is implicated in unfavorable remodeling of the left ventricle during acute myocardial infarction (AMI). Both DNA damage and p53 play important roles in regulating apoptosis. Expression patterns of apoptotic regulating genes such as p53, bax, and bcl-2 highlight the importance of inhibiting ventricle remodeling and subsequent injuries. In the present study, serum levels of p53 and 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as p53, bax, and bcl-2 expression were examined after the onset of AMI in Iranian patients. Serum levels of p53 and 8-OHdG were measured by enzyme-linked immunosorbent assay (ELISA) and the presence of p53 protein and mRNA expression of p53, bax, and bcl-2 were analyzed by Western blotting and real time RT-PCR methods respectively. In patients presenting with AMI, serum levels of p53 and 8-OHdG were increased in comparison to healthy controls. Likewise, transcripts of p53 and bax were also elevated in patients while bcl-2 was decreased. Collectively, our data suggest the novel use of p53 and 8-OHdG as markers of apoptosis and DNA damage following AMI. Our results also revealed that apoptosis occurs in concert with an up-regulation of p53 and bax and a down-regulation of bcl-2 which may suggest a possible therapeutic intervention in patients recovering from AMI.© Versita Sp. z o.o.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of p53, bax, bcl2, and 8-OHdG in human acute myocardial infarction

et al. 2010

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“…Among the wide spectrum of apoptosis regulatory proteins tested in our studies, the proapoptotic protein Bax was found to be overexpressed in H37-overexpressing lung cancer cells, with concomitant triggering of the mitochondrial apoptotic pathways, including caspase-9 and caspase-3 activations. A major regulation of the apoptotic death signal resides with the bcl-2/bax genes, the former an apoptosis-suppressing and the latter an apoptosispromoting protein (29). Bax and Bcl-2 can form heterodimers, and overexpression of one antagonizes the other's effect; p53 functions, in part, by regulating the ratio of Bax/Bcl-2.…”

Section: Discussionmentioning

confidence: 99%

3p21.3 Tumor Suppressor Gene H37/Luca15/RBM5 Inhibits Growth of Human Lung Cancer Cells through Cell Cycle Arrest and Apoptosis

Razfar

Delgado

et al. 2006

Cancer Research

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Deletion at chromosome 3p21.3 is the earliest and the most frequently observed genetic alteration in lung cancer, suggesting that the region contains tumor suppressor gene(s) (TSG). Identification of those genes may lead to the development both of biomarkers to identify high-risk individuals and novel therapeutics. Previously, we cloned the H37/Luca15/RBM5 gene from 3p21.3 and showed its TSG characteristics. To investigate the physiologic function of H37 in the lung and its mechanism of tumor suppression, we have stably transfected H37 into A549 non-small cell lung cancer cells. A549/H37 cells show significant growth inhibition compared with the vector controls by in vitro and in vivo cell proliferation assays. Using this lung cancer cell model, we have found that the molecular mechanism of H37 tumor suppression involves both cell cycle (G 1 ) arrest and apoptosis. To further define H37's function in cell cycle/apoptotic pathways, we investigated differential expression profiles of various cell cycle and apoptosis regulatory proteins using Western blot analysis. Both cyclin A and phophorylated RB levels were decreased in H37-transfected cells, whereas expression of Bax protein was increased. Mitochondrial regulation of apoptosis further downstream of Bax was investigated, showing change in the mitochondrial membrane potential, cytochrome c release into the cytosol, and enhanced caspase-9 and caspase-3 activities. We also report that H37 may mediate apoptosis in a p53-independent manner, and Bax knockdown by small interfering RNA suggests Bax plays a functional role downstream of H37. Lastly, we proposed a tumor suppression model of H37 as a post-transcriptional regulator for cell cycle/apoptotic-related proteins.

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“…Bcl-2 downregulation is an early sign for the onset of apoptotic process. [38][39][40][41][42] Overexpression of Bcl-2 protein in PC seems to be responsible for the resistance to chemotherapy and radiotherapy and enhances the tumor metastatic potential; therefore, its downregulation upon treatment with FPA-306 is an important finding which could be further exploited in designing a rational combination chemotherapy regimen.…”

Section: Discussionmentioning

confidence: 99%

A novel copper complex of 3‐benzoyl‐α methyl benzene acetic acid with antitumor activity mediated via cyclooxygenase pathway

Ahmed

Adsule

Ali

et al. 2006

Intl Journal of Cancer

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Pancreatic cancer (PC) is characterized as one of the deadliest malignancies and its treatment is a great challenge to clinical oncologists. Expression of COX-2 is detectable in 75% of PCs among which 50% showed overexpression, suggesting the importance of COX-2 enzyme and its metabolic product prostaglandin E2 (PGE 2 ) in PC. Here the authors report the synthesis and biological activity of a novel COX-2 inhibitor, FPA-306, and its effects on PC cells with different levels of COX-2 expression. Using MTT assay, the authors found a significant growth inhibition of BxPC-3 cells treated by FPA-306 with an IC 50 of 10 lmol/ L, which was lower than that of ketoprofen (IC 50 5 35.4 lmol/L) and celecoxib (IC 50 > 100 lmol/L). There was no such effect found in MIAPaCa cell line, which does not express COX-2. The authors also found dose dependent reduction in cell survival and induction of apoptosis by FPA-306 treatment in BxPC-3 cells but not in MIAPaCa cells. These results were correlated with apoptosis data and secreted PGE 2 levels. The molecular modeling of FPA-306 in the COX-2 active site showed that FPA-306 is potentially able to inhibit the activity of enzyme by blocking the active site, thereby resulting in decreased PGE 2 production. The authors also found a significant reduction of COX-2 at the mRNA and protein levels together with downregulation of NF-jB DNA binding activity and its downstream genes, Bcl-2 and survivin. These results suggest that FPA-306 is an effective and potent agent in inhibiting the growth of PC cells. ' 2006 Wiley-Liss, Inc.Key words: pancreatic cancer cells; cyclooxygenase-2; NSAIDS; prostaglandin E 2 Pancreatic cancer (PC) is the fourth leading cause of cancer related death in the United States. An estimated 33,730 individuals will be diagnosed with PC in the year of 2006, with an almost similar incidence rate among males and females. 1 PC is relatively resistant to all currently available therapeutic approaches including radiotherapy and chemotherapy. Palliative care is the only option because most of the patients are also not suitable for surgery at the time of diagnosis. Thus, delayed diagnosis partly due to indolent nature of pancreatic tumor progression and lack of effective therapy results in limited survival.From a mechanistic point of view, several molecular pathways have been identified such as Ras-Raf-MEK-ERK, PI3K/Akt and NF-jB pathway that are believed to be important in the development, progression and metastasis of PC. In addition, the involvement of cyclooxygenase (COX) and lipoxygenase family of enzymes in the development and progression of PC has been appreciated recently. 2 The COX family of enzymes catalyzes the ratelimiting step in conversion of arachidonic acid into prostaglandins. 3 Three isoforms of COX enzyme have been reported-COX-1, COX-2 and COX-3. 4 COX-1 is constitutively expressed in many tissues where it serves as house keeping gene whereas COX-2 is an inducible enzyme that is rapidly transcribed, perhaps regulated by NF-jB and other transcription factor...

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Apoptosis

Cited by 73 publications

References 31 publications

The role of p53, bax, bcl2, and 8-OHdG in human acute myocardial infarction

The role of p53, bax, bcl2, and 8-OHdG in human acute myocardial infarction

3p21.3 Tumor Suppressor Gene H37/Luca15/RBM5 Inhibits Growth of Human Lung Cancer Cells through Cell Cycle Arrest and Apoptosis

A novel copper complex of 3‐benzoyl‐α methyl benzene acetic acid with antitumor activity mediated via cyclooxygenase pathway

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