Expression of p53 synergistically augments caspases-mediated apoptosis induced by replication-competent adenoviruses in pancreatic carcinoma cells

Takei, Yoshiyuki; Okamoto, Shinya; Kawamura, Kiyoko; Jiang, Yuanyuan; Morinaga, Takao; Shingyoji, Masato; Sekine, Ikuo; Kubo, Shuji; Tada, Yuji; Shimada, Hideaki; Hiroshima, Kenzo; Yamaguchi, Naoto; Tagawa, Masatoshi

doi:10.1038/cgt.2015.33

Cited by 7 publications

(3 citation statements)

References 22 publications

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“…The development of multiple complications is closely related to degree to which apoptosis is stimulated. The process of apoptosis is very complex and usually influenced by the caspase and the Bcl-2 family of factors ( 7 , 8 ). Caspase-3 plays an important role in the protease cascade cleavage, which can hydrolyze apoptotic proteins in cells, promoting apoptosis of such cells.…”

Section: Discussionmentioning

confidence: 99%

Correlation of expression levels of caspase-3 and Bcl-2 in alveolar lavage fluid in neonatal respiratory distress syndrome and prognosis

Lin

Wang

2018

Exp Ther Med

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This study was designed to investigate the correlation between expression levels of cysteine aspartic protease-3 (caspase-3) and B-cell lymphoma gene-2 (Bcl-2) proteins in alveolar lavage fluid and the prognosis of infants with neonatal respiratory distress syndrome (RDS). A total of 150 infants with neonatal RDS undergoing alveolar lavages were divided into four groups: RDS1 (group A, n=42), RDS2 (group B, n=38), RDS3 (group C, n=38) and RDS4 (group D, n=32) according to their thoracic X-ray film grading. The oxygen uptake score, oxygenation saturation, mean airway pressure and expression levels of caspase-3 and Bcl-2 in alveolar lavage fluid of the infants in the four groups were measured and compared. Our results showed higher grading by thoracic X-rays in patients with increased oxygen uptake score, oxygenation index, mean airway pressure, caspase-3 expression level, hospital stay, complications and death rates in all groups; however, the expression levels of Bcl-2 were decreased in those cases, and the differences had statistical significance among the four groups (P<0.05). Analyses for correlation showed a caspase-3 positive area that was positively correlated with oxygen uptake score, oxygenation index and mean airway pressure (P<0.05); and a Bcl-2 expression level that was negatively correlated with oxygen uptake score, oxygenation index and mean airway pressure (P<0.05). Based on our findings, the severity of neonatal RDS is positively correlated with the concentration of caspase-3 in alveolar lavage fluid, and negatively correlated with the expression level of Bcl-2.

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Section: Discussionmentioning

confidence: 99%

Correlation of expression levels of caspase-3 and Bcl-2 in alveolar lavage fluid in neonatal respiratory distress syndrome and prognosis

Lin

Wang

2018

Exp Ther Med

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“… 2015 ; Takei et al. 2015 ). Caspase-3 plays an important role in the protease cascade cleavage, which can hydrolyze apoptotic proteins in cells, promoting the apoptosis of such cells.…”

Section: Discussionmentioning

confidence: 99%

Zinc-nanoparticles alleviate the ovarian damage induced by bacterial lipopolysaccharide (LPS) in pregnant rats and their fetuses

El-Beltagy,

Bakr,

Mekhaimer

et al. 2023

Histochem Cell Biol

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Lipopolysaccharide (LPS) is an endotoxin derived from the cell wall of Gram-negative bacteria. LPS exposure during early gestation is associated with adverse effects on the placenta as well as on developmental outcomes, including embryonic resorption, fetal death, congenital teratogenesis, and fetal growth retardation. This work aimed to explore the adverse effects of LPS injected at an early stage of gestation on the gonads of pregnant rats and the ovaries of their pups and the role of zinc nanoparticles (Zn-NPs) against these adverse effects. Twenty-four pregnant rats were used in this study. They were divided at gestation day 4 into four groups (n = 6): control, Zn-NPs (20 mg/kg orally from gestation day E14 till the end of weaning), LPS (50 µg/kg at gestation days E7 and E9), and LPS + Zn-NPs group. The body weight and placenta weight were recorded at gestational day 16. At postnatal day 21 (weaning), the mothers rats and their offspring were sacrificed and immediately dissected to remove the ovaries and uteri from the mothers and the ovaries from their offspring for subsequent biochemical, histological, and immunohistochemical investigations. The obtained results revealed that LPS exposure during early gestation caused severe histopathological alterations in the placenta, uterus, and ovaries of mothers, as well as in the ovaries of their pups. Also, the uterine and ovarian sections displayed a positive reaction for caspase-3 antibody and a negative reaction for Bcl-2 antibody, which reflects the apoptotic effect of LPS. Additionally, remarkable reductions in the levels of antioxidants (superoxide dismutase and catalase) and significant increases in malondialdehyde (MDA) levels were recorded in the serum of LPS-treated mothers and in the ovarian tissues of their offspring. Further biochemical analysis of the ovarian tissues from LPS-maternally treated offspring showed a significant increase in the levels of caspase-3, TNF-α, and TGF-β1, but a significant decrease in the level of IGF-1. On the other hand, treatment of mothers with Zn-NPs from day 14 of gestation until the weaning day (21st day postnatal) successfully ameliorated most of the deleterious histopathological, immunohistochemical, and biochemical changes induced by LPS. Graphical abstract

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“…These data clearly showed 5/35 fiber-modified adenoviral vector had efficient infection for renal cancer cells in our experiment, which was consistent with reports from different investigators. 10,23,24 Hep27 is a short-chain dehydrogenase/reductase, which is synthesized in human hepatoblastoma HepG2 cells following growth arrest induced by butyrate treatment. 15 Hep27 could translocate to the nucleus and bind to Mdm2, resulting in the attenuation of Mdm2-mediated p53 degradation.…”

Section: Discussionmentioning

confidence: 99%

Selective effects of a fiber chimeric conditionally replicative adenovirus armed with hep27 gene on renal cancer cell

Lin

Qian

Liu

et al. 2016

Cancer Biology & Therapy

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ASBTARCTAdenoviruses mediated cancer gene therapies are widely investigated and show a promising effect on cancer treatment. However, efficient gene transfer varies among different cancer cell lines based on the expression of coxsakie adenovirus receptor (CAR). Hep27, a member of dehydrogenase/reductase (SDR) family, can bind to Mdm2, resulting in the attenuation of Mdm2-mediated p53 degradation. Here we constructed a fiber chimeric adenovirus carrying hep27 gene (F5/35-ZD55-Hep27), in which the fiber protein of 5-serotype adenovirus (Ad5) was substituted by that of 35-serotype adenovirus (Ad35), aiming to facilitate the infection for renal cancer cells and develop the role of hep27 in cancer therapy. We evaluated the CAR and CD46 (a membrane cofactor protein for Ad35) expression in four kinds of renal cancer cells and assessed the relationship between receptors and infection efficiency. 5/ 35 fiber-modified adenovirus had a much promising infectivity compared with Ad5-based vector in renal cancer cells. F5/35-ZD55-Hep27 had enhanced antitumor activity against human renal cancer cells compared to the other groups. Further, hep27 mediated p53 and cleaved-PARP upregulation and mdm2 downregulation was involved and caused increased apoptosis. Moreover, F5/35-ZD55-Hep27 significantly suppressed tumor growth in subcutaneous renal cancer cell xenograft models. Our data demonstrated that 5/35 fiber-modified adenovirus F5/35-ZD55-Hep27 transferred into renal cancers efficiently and increased p53 to induce cancer cell apoptosis. Thus 5/35 fiber-modified adenoviral vector F5/35-ZD55-Hep27 might a promising vector and antitumor reagent for renal cancer gene therapy.

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Expression of p53 synergistically augments caspases-mediated apoptosis induced by replication-competent adenoviruses in pancreatic carcinoma cells

Cited by 7 publications

References 22 publications

Correlation of expression levels of caspase-3 and Bcl-2 in alveolar lavage fluid in neonatal respiratory distress syndrome and prognosis

Correlation of expression levels of caspase-3 and Bcl-2 in alveolar lavage fluid in neonatal respiratory distress syndrome and prognosis

Zinc-nanoparticles alleviate the ovarian damage induced by bacterial lipopolysaccharide (LPS) in pregnant rats and their fetuses

Selective effects of a fiber chimeric conditionally replicative adenovirus armed with hep27 gene on renal cancer cell

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