• Title, Summary, Keyword: caspase-3

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Immunohistochemical Expression of Caspase 3 and Its Relationship with p53 Expression in Endometrial Cancers

  • Lee, Kyung-Enn
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.307-310
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    • 2010
  • Apoptosis is an important significance in the pathogenesis of cancer. Caspase 3 and p53 have been identified as important members of the apoptosis related proteins. This study was performed to define roles of caspase 3 expression and its relationship with p53 expression in endometrial cancers by immunohistochemistry. Immunoreactivity for caspase 3 was found in 13 (65.0%) out of 20 endometrial hyperplasia cases and 8 (36.4%) out of 22 endometrial cancers. Seven (87.5%) of the 8 cases with a positive caspase 3 immunoreactivity showed a positive p53 expression in 22 endometrial cancers. There were no significant associations between caspase 3 and p53 expressions. These findings suggest that caspase 3 expression might be associated with carcinogenesis of endometrial cancers. Further studies are needed to define the relationship between caspase 3 and p53 and apoptosis for examining the mechanisms of tissue-specific apoptosis related protein.

RADIOPROTECTIVE EFFECT OF ALGIN-OLIGOSACCHARIDE THROUGH MEASURING CASPASE-3 AND CASPASE-9 IN MICE

  • Choi, Seong-Kwan;Jung, Woon-Kwan;Lee, Kyu-Soo;Jang, Young-Il;Dong, Kyeong-Rae
    • Journal of Radiation Protection and Research
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    • v.32 no.4
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    • pp.134-139
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    • 2007
  • In order to find out the Radioprotective effect of algin-oligosaccharide(AOS), this study, with a mouse of which whole frame irradiated by 3 Gy radiation once, measured caspase-3 and caspase-9 amid cell signaling connected to apoptosis in order to observe cell activation. In Caspase-3 and Caspase-9 test for observing cell activation, both of Caspase-3 and Caspase-9 showed highly increased O.D. value in the irradiation control group, while the whole groups treated with algin-oligosaccharide before or after irradiation indicated lower O.D. value than the irradiation control group, especially showed big difference in 7 day's treatment group of before irradiation (P<0.001). It confirmed that Caspase generation was restrained in AOS treatment group. Consequently, this study inquired into the fact that algin-oligosaccharide with superior antioxidant activity performed radiation protection by inducing restraint of Caspase generation and confirmed that natural product with less chemical toxicity was able to be applied as radioprotector.

Effect of Hypoxia on the Signal Transduction of Apoptosis in Osteoblasts (저산소 상태에서 조골세포 고사의 신호전달 기전)

  • Park, Young-Joo;Oh, Soh-Taek;Kang, Kyung-Hwa;Kim, Sang-Cheol
    • The korean journal of orthodontics
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    • v.33 no.6
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    • pp.453-463
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    • 2003
  • Mammalian cell is critically dependent on a continuous supply of oxygen. Even brief periods of oxygen deprivation can result in profound cellular damage. The aim of this study was to examine the possible mechanism of apoptosis in response to hypoxia in MC3T3E1 osteoblasts. MC3T3El osteoblasts under hypoxic conditions ($2\%$ oxygen) resulted in apoptosis in a time-dependent manner, determined by DNA fragmentation assay and nuclear morphology, stained with fluorescent dye (Hoechst 33258) Pretreatment with Z-VAD-FMK, a pancaspase inhibitor, or Z-DEVD-CHO, a specific caspase-3 inhibitor, suppressed the DNA ladder in response to hypoxia in a concentration dependent manner. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-l activity (YVADase) was detected. To confirm what caspases were involved in apoptosis, western blot analysis was performed using an anticaspase-3 or 6 antibody. The 17-kDa protein, that corresponds to the active products of caspase-3 and the 20-kDa protein of the active protein of caspase-6 were generated in hypoxia-challenged lysates, in which the full length forms of caspase-3 and 6 were evident. With a time course similar to caspase-3 and 6 activation, hypoxic stress also caused the cleavage of Lamin A, typical of caspase-6 activity. In addition, the hypoxic stress elicited the release of cytochrome c into the cytosol during apoptosis. These findings suggested that the activation of caspases accompanied by a cytochrome c release in response to hypoxia was involved in apoptotic cell death in MC3T3E1 osteoblasts.

Caspase-2 mediates triglyceride (TG)-induced macrophage cell death

  • Lim, Jaewon;Kim, Hyun-Kyung;Kim, Sung Hoon;Rhee, Ki-Jong;Kim, Yoon Suk
    • BMB Reports
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    • v.50 no.10
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    • pp.510-515
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    • 2017
  • Triglyceride (TG) accumulation causes macrophage cell death, which affects the development of atherosclerosis. Here, we examined whether caspase-2 is implicated in TG-induced macrophage cell death. We found that caspase-2 activity is increased in TG-treated THP-1 macrophages, and that inhibition of caspase-2 activity drastically inhibits TG-induced cell death. We previously reported that TG-induced macrophage cell death is triggered by caspase-1, and thus investigated the relationship between caspase-2 and caspase-1 in TG-induced macrophage cell death. Inhibition of caspase-2 activity decreased caspase-1 activity in TG-treated macrophages. However, caspase-1 inhibition did not affect caspase-2 activity, suggesting that caspase-2 is upstream of caspase-1. Furthermore, we found that TG induces activation of caspase-3, -7, -8, and -9, as well as cleavage of PARP. Inhibition of caspase-2 and -1 decreased TG-induced caspase-3, -7, -8, and -9 activation and PARP cleavage. Taken together, these results suggest that TG-induced macrophage cell death is mediated via the caspase-2/caspase-1/apoptotic caspases/PARP pathways.

Induction of Caspase-3 Dependent Apoptosis in Human Ovarian Cancer SK-OV-3 Cells by Genistein

  • Choi, Eun-Jeong;Kim, Tae-Hee;Kim, Gun-Hee;Chee, Kew-Mahn
    • Food Science and Biotechnology
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    • v.17 no.1
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    • pp.216-218
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    • 2008
  • The present study was designed to determine how the phytochemical genistein activates caspase-3 to cause cell cycle arrest and apoptosis. When human ovarian cancer SK-OV-3 cells were treated with $200\;{\mu}M$ genistein for 24 hr, cell growth decreased significantly (p<0.05). Conversely, genistein treatment significantly increased cytotoxicity (measured as lactate dehydrogenase release) under the same conditions (p<0.05). To elucidate the mechanism behind the induction of apoptosis by genistein, we studied the cell cycle and caspase-3 activation. When cells were treated with genistein, the population of cells in sub-G1 phase increased by 44.2% compared to untreated cells. Genistein caused decrease in precursor caspase-3, increase in cleaved caspase-3 and a significant increase in caspase-3 activity (p<0.05). Therefore, genistein may induce apoptosis via caspase-3 activation. However, high-dose genistein treatment must be viewed with caution because of its potential cytotoxicity.

S-allylcysteine-mediated Activation of Caspases and Inactivation of PARP to Inhibit Proliferation of HeLa (S-allylcysteine 매개 caspases의 활성화 및 PARP의 불활성화를 통한 HeLa 세포주의 증식 억제효과)

  • Kim, Hyun Hee;Kong, Il-Keun;Min, Gyesik
    • Journal of Life Science
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    • v.27 no.2
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    • pp.164-171
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    • 2017
  • Our previous study suggested that S-allylcysteine (SAC) inhibits the proliferation of the human cervical cancer cell line, HeLa, at least in part through the induction of apoptosis and cell cycle arrest. To further analyze the specific molecular mechanism(s) by which SAC mediates its antiproliferative effects, this study examined the role of SAC in regulating the protein expression of initiator caspase (caspase-9), effector caspases (caspase-3 and caspase-7), and poly-ADP-ribose polymerase (PARP) in HeLa. Western blot analysis showed that when cells were treated with 50 mM SAC for 48 hr, the expression of procaspase-3, -7, and -9 and PARP was reduced by 94%, 38%, 95%, and 64%, respectively, as compared to the untreated control. In contrast, the expression of caspase-3, -7, and -9 and cleaved-PARP was markedly increased by SAC treatment. The SAC-mediated changes in the expression of these proteins were correlated with the concomitant inhibition of cellular proliferation by SAC. The cell proliferation assay showed that HeLa treatment with more than 20 mM SAC for 6-48 hr resulted in both concentration- and time-dependent inhibition of cellular proliferation. These results indicate that the SAC-induced antiproliferative effect in HeLa may be mediated at least in part through the activation of caspase-9, followed by the activation of caspase-3 and caspase-7 as well as the inactivation of PARP, thus leading to cellular apoptosis.

A Possible Physiological Role of Caspase-11 During Germinal Center Reaction

  • Kang, Shin-Jung
    • Animal cells and systems
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    • v.12 no.3
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    • pp.127-136
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    • 2008
  • Caspase-11 has been known as a dual regulator of cytokine maturation and apoptosis. Although the role of caspase-11 under pathological conditions has been well documented, its physiological role has not been studied much. In the present study, we investigated a possible physiological function of caspase-11 during immune response. In the absence of caspase-11, immunized spleen displayed increased cellularity and abnormal germinal center structure with disrupted microarchitecture. The rate of cell proliferation and apoptosis in the immunized spleen was not changed in the caspase-11-deficient mice. Furthermore, the caspase-11-deficient peritoneal macrophages showed normal phagocytotic activity. However, caspase-11-/-splenocytes and macrophages showed defective migrating capacity. The dysregulation of cell migration did not seem to be mediated by caspase-3, interleukin-$1{\alpha}$ or interleukin-$1{\beta}$ which acts downstream of caspase-11. These results suggest that a direct regulation of immune cell migration by caspase-11 is critical for the formation of germinal center microarchitecture during immune response. However, humoral immunity in the caspase-11-deficient mice was normal, suggesting the formation of germinal center structure is not essential for the affinity maturation of the antibodies.

Abrin Induces HeLa Cell Apoptosis by Cytochrome c Release and Caspase Activation

  • Qu, Xiaoling;Qing, Liuting
    • BMB Reports
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    • v.37 no.4
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    • pp.445-453
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    • 2004
  • We identified apoptosis as being a significant mechanism of toxicity following the exposure of HeLa cell cultures to abrin holotoxin, which is in addition to its inhibition of protein biosynthesis by N-glycosidase activity. The treatment of HeLa cell cultures with abrin resulted in apoptotic cell death, as characterized by morphological and biochemical changes, i.e., cell shrinkage, internucleosomal DNA fragmentation, the occurrence of hypodiploid DNA, chromatin condensation, nuclear breakdown, DNA single strand breaks by TUNEL assay, and phosphatidylserine (PS) externalization. This apoptotic cell death was accompanied by caspase-9 and caspase-3 activation, as indicated by the cleavage of caspase substrates, which was preceded by mitochondrial cytochrome c release. The broad-spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-fmk), prevented abrin-triggered caspase activation and partially abolished apoptotic cell death, but did not affect mitochondrial cytochrome c release. These results suggest that the release of mitochondrial cytochrome c, and the sequential caspase-9 and caspase-3 activations are important events in the signal transduction pathway of abrin-induced apoptotic cell death in the HeLa cell line.

Ginsenoside Rh2 Induces Apoptosis via Activation of Caspase-1 and -3 and Up-Regulation of Bax in Human Neuroblastoma

  • Kim, Young-Soak;Jin, Sung-Ha
    • Archives of Pharmacal Research
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    • v.27 no.8
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    • pp.834-839
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    • 2004
  • In human neuroblastoma SK-N-BE(2) cells undergoing apoptotic death induced by ginsenos-ide Rh2, a dammarane glycoside that was isolated from Panax ginseng C. A. Meyer, caspase-1 and caspase-3 were activated. The expression of Bax was increased in the cells treated with ginsenoside Rh2, whereas Bcl-2 expression was not altered. Treatment with caspase-1 inhibi-tor, Ac-YVAD-CMK, or caspase-3 inhibitor, Z-DEVD-FMK, partially inhibited ginsenoside Rh2-induced cell death but almost suppressed the cleavage of the 116 kDa PARP into a 85 kDa fragment. When the levels of p53 were examined in this process, p53 accumulated rapidly in the cells treated early with ginsenoside Rh2. These results suggest that activation of caspase-1 and -3 and the up-regulation of Bax are required in order for apoptotic death of SK-N-BE(2) cells to be induced by ginsenoside Rh2, and p53 plays an important role in the pathways to promote apoptosis.

The Caspase-3 and c-myc Expressions in Completely Resected Non-small Cell Lung Cancer and Its Prognostic Significance (완전 절제된 원발성 비소세포 폐암에서 Caspase-3와 c-myc 단백의 발현과 임상 예후)

  • Cho, Deog-Gon;Cho, Kyu-Do;Kang, Chul-Ung;Jo, Min-Seop;Yoo, Jin-Young;Ahn, Myeong-Im;Kim, Chi-Hong;Shim, Byoung-Yong;Kim, Sung-Whan;Kim, Hoon-Kyo
    • Journal of Chest Surgery
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    • v.41 no.4
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    • pp.447-456
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    • 2008
  • Background: Caspase-3 is a cysteine protease that plays a major role in the process of apoptotic cell death. The dysregulated expression of c-myc contributes to the tumorigenesis in a variety of human cancers. The aim of this study was to investigate the expressions of caspase-3 and c-myc and their significances as prognosis markers in patients with completely resected non-small cell lung cancer (NSCLC). Material and Method: A total 130 consecutive patients who had undergone complete resection without pre-operative radio-therapy or chemotherapy between May 1996 and December 2003 for NSCLC were retrospectively reviewed. The median follow-up period of the patients was 50 months (range: $3{\sim}128$ months). The expressions of caspase-3 and c-myc were immuno-histochemically examined, and these were correlated with the clinico-pathologic data. Result: The prevalence of caspase-3 and c-myc expressions in the patients was 68% (88/130) and 59% (77/130), respectively. Significant association was found between the frequency of the expressions of caspase-3 and c-myc (p=0.025). The caspase-3 and c-myc expressions were not significantly associated with the prognosis in all the patients. However, according to stages, a positive caspase-3 expression was significantly correlated with a favorable prognosis for patients with stage IIIa disease (median survival period: 35 months vs. 10 months, p=0.021). Multivariate analysis showed the pathologic stage to be significantly correlated with a good prognosis in all the patients (p=0.024), and with a positive caspase-3 expression, well differentiated tumor and negative neuronal invasion in the patients with stage llla disease (p=0.005, p=0.003, p=0.004, respectively). Conclusion: Caspase-3 and c-myc were frequently expressed in NSCLC, suggesting its possible involvement in tumor development. The caspase-3 expression, as determined with performing immunohistochemical staining, may be a favorable prognostic indicator in patients with completely resected NSCLC an advanced stage (IIIa).