• 대한두경부종양학회지
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• 제22권1호
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• pp.15-22
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• 2006

Objectives: The salivary gland tumor shows heterogeneity in histologic patterns and biological behavior. The aim of this study is to elucidate the relationships between apoptosis and expressions of apoptosis-related factors(bcl-2, bax, M30), p53 and MIB-1 in the salivary gland tumors. Methods: Immunohistochemical stains for apoptosis-related factors, p53 and MIB-1 and TUNEL study for apoptosis were performed in 46 cases of salivary gland tumors 02 benign and 34 malignant). Results: Twenty(43.5%) of 46 cases showed positive reaction for apoptosis, and the expression rates of bcl-2, bax, M30, p53 and MIB-1 were 85.3%, 68.8%, 65.9%, 39.1% and 26.1%, respectively. A significant difference between benign and malignant tumors was only noted in MIB-1 expression(p=0.0167). In malignant tumors, apoptosis showed no significant relationships to expressions of apoptosis-related factors. There were inverse relationships between p53 and bcl-2 expression(p=0.0375), and between M30 and MIB-1 expressions(p=0.0379). No significant differences of apoptosis, bcl-2, bax, M30, p53 and MIB-1 expression rates according to the tumor size, lymph node status, recurrence and survival were found. Conclusion: In the development of benign and malignant salivary gland tumors, apoptosis might be associated, however, apoptosis and expressions of apoptosis-related factors seemed to be not reliable prognostic factors in malignant salivary gland tumors.

• 생명과학회지
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• 제8권1호
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• pp.51-59
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• 1998

Ursolic acid(UA)의 apoptosis 유도능을 F9 생쥐 기형암종세포를 대상으로 조사하였다. UA는 피부암화의 억제, tumor의 분화유도, tumor promotion의 억제 등의 항암 효과를 나타내는 pentacyclic triterpene acid로 물질로 알려져 있다. UA를 F9세포에 처리하였을 때 농도비례로 성장억제를 나타냈다. 또한 apoptosis과정에서 관찰되는 전형적인 DNA 분절을 관찰할 수 있었고, 전자현미경을 이용한 세포의 미세구조를 관찰한 결과, 역시 apoptosis과정에서 관찰되는 전형적인 형태인 염색질 응축, 핵의 분절들을 관찰할 수 있어, UA에 의한 항암 효과는 apoptosis에 의한 것임을 시사한다. UA에 의한 apoptosis는 단백질 합성저해제인 cycloheximide에 의해 저해됨을 관찰할 수 있었다. UA를 F4쎄포에 처리한 후 oncogene의 발현양상을 조사한 결과, c-myc과 laminin B1은 apoptosis과정동안 점점 감소하고 c-jun은 증가함을 관찰할 수 있었다. 이상의 결과로서 UA에 의한 F9 세포의 apoptosis에는 새로운 단백질의 합성이 요구되며, c-myc 및 laminin의 발현 감소와 c-jumd의 발현 증가가 관여하고 있음을 시사한다.

• Tuberculosis and Respiratory Diseases
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• 제81권2호
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• pp.132-137
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• 2018

Background: The pathophysiology of chronic obstructive pulmonary disease (COPD) includes inflammation, oxidative stress, an imbalance of proteases and antiproteases and apoptosis which has been focused on lately. Abnormal apoptotic events have been demonstrated in both epithelial and endothelial cells, as well as in inflammatory cells including neutrophils and lymphocytes in the lungs of COPD patients. An increased propensity of activated T lymphocytes to undergo apoptosis has been observed in the peripheral blood of COPD patients. Therefore, the apoptosis of T lymphocytes without activating them was investigated in this study. Methods: Twelve control subjects, 21 stable COPD patients and 15 exacerbated COPD patients were recruited in the study. The T lymphocytes were isolated from the peripheral blood using magnetically activated cell sorting. Apoptosis of the T lymphocytes was assessed with flow cytometry using Annexin V and 7-aminoactinomycin D. Apoptosis of T lymphocytes at 24 hours after the cell culture was measured so that the T lymphocyte apoptosis among the control and the COPD patients could be compared. Results: Stable COPD patients had increased rates of $CD4^+$ T lymphocyte apoptosis at 24 hours after the cell culture, more than the $CD4^+$ T lymphocyte apoptosis which appeared in the control group, while the COPD patients with acute exacerbation had an amplified response of $CD4^+$ T lymphocyte apoptosis as well as of $CD8^+$ T lymphocyte apoptosis at 24 hours after the cell culture. Conclusion: Stable COPD patients have more apoptosis of $CD4^+$ T lymphocytes, which can be associated with the pathophysiology of COPD in stable conditions.

• Molecules and Cells
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• 제27권5호
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• pp.533-538
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• 2009

Heat shock protein 27 (Hsp27) is a molecular chaperone protein which regulates cell apoptosis by interacting directly with the caspase activation components in the apoptotic pathways. With the assistance of the Tat protein transduction domain we directly delivered the Hsp27 into the myocardial cell line, H9c2 and demonstrate that this protein can reverse hypoxia-induced apoptosis of cells. In order to characterize the contribution of Hsp27 in blocking the two major apoptotic pathways operational within cells, we exposed H9c2 cells to staurosporine and cobalt chloride, agents that induce mitochondria-dependent (intrinsic) and -independent (extrinsic) pathways of apoptosis in cells respectively. The Tat-Hsp27 fusion protein showed a greater propensity to inhibit the effect induced by the cobalt chloride treatment. These data suggest that the Hsp27 predominantly exerts its protective effect by interfering with the components of the extrinsic pathway of apoptosis.

• BMB Reports
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• 제35권1호
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• pp.28-40
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• 2002

Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-${\kappa}B$ activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-${\kappa}B$ and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which mayor may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-${\kappa}B$ controls apoptosis.

• Biomolecules & Therapeutics
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• 제22권5호
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• pp.384-389
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• 2014

Adiponectin, an adipokine predominantly secreted from adipose tissue, exhibits diverse biological responses, including metabolism of glucose and lipid, and apoptosis in cancer cells. Recently, adiponectin has been shown to modulate autophagy as well. While emerging evidence has demonstrated that autophagy plays a role in the modulation of proliferation and apoptosis of cancer cells, the role of autophagy in apoptosis of cancer cell caused by adiponectin has not been explored. In the present study, we demonstrated that globular adiponectin (gAcrp) induces both apoptosis and autophagy in human hepatoma cell line (HepG2 cells) and breast cancer cells (MCF-7), as evidenced by increase in caspase-3 activity, Bax, microtubule-associated protein light chain 3-II (LC3 II) protein levels, and autophagosome formation. Interestingly, gene silencing of LC3B, an autophagy marker, significantly enhanced gAcrp-induced apoptosis in both HepG2 and MCF-7 cell lines, whereas induction of autophagy by rapamycin, an mTOR inhibitor, significantly prevented gAcrp-induced apoptosis in hepatoma cells HepG2. Furthermore, modulation of autophagy produced similar effects on gAcrp-induced Bax expression in HepG2 cells. These results implicate that induction of autophagy plays a regulatory role in adiponectin-induced apoptosis of cancer cells, and thus inhibition of autophagy would be a novel promising target to enhance the efficiency of cancer cell apoptosis by adiponectin.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5895-5900
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• 2013

Dictamnine (Dic) has the ability to exert cytotoxicity in human cervix, colon, and oral carcinoma cells and dihydroartemisinin (DHA) also has potent anticancer activity on various tumour cell lines. This report explores the molecular mechanisms by which Dic treatment and combination treatment with DHA and Dic cause apoptosis in human lung adenocarcinoma A549 cells. Dic treatment induced concentration- and time-dependent cell death. FCM analysis showed that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which loss of mitochondrial membrane potential (${\Delta}{\Psi}m$) was not involved. In addition, inhibition of caspase-3 using the specific inhibitor, z-DQMD-fmk, did not attenuate Dic-induced apoptosis, implying that Dic-induced caspase-3-independent apoptosis. Combination treatment with DHA and Dic dramatically increased the apoptotic cell death compared to Dic alone. Interestingly, pretreatment with z-DQMD-fmk significantly attenuated DHA and Dic co-induced apoptosis, implying that caspase-3 plays an important role in Dic and DHA co-induced cell apoptosis. Collectively, we found that Dic induced S phase cell cycle arrest at low concentration and cell apoptosis at high concentration in which mitochondria and caspase were not involved and DHA enhanced Dic induced A549 cell apoptosis via a caspase-dependent pathway.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권2호
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• pp.94-100
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• 2006

Purpose: This study was done to confirm the role of NF-$\kappa$B in cisplatin-induced apoptosis of oral squamous cell carcinoma. Materials and Methods: Five cell lines originated from different oral cancer patients were tested for the apoptosis by the treatment of cisplatin. These cells showed different degree of cisplatin-resistance and the order is OSCC-2>OSCC-3>OSCC-5> OSCC-1>OSCC-4. OSCC-2 and OSCC-4 cells were assayed for the apoptosis by measuring DNA fragmentation and TUNEL staining after cisplatin treatment. While OSCC-4 cells showed apoptosis, OSCC-2 cells showed no or very slight apoptosis by cisplatin treatment. Next, It was determined whether NF-$\kappa$B activation is required in mediating cisplatin-induced apoptosis of OSCC-4. Result: The result was that elevated NF-$\kappa$B activity mediated cisplatin-induced apoptosis. Conclusion: In conclusion, these findings suggest that NF-$\kappa$B activation is essential to cisplatin-induced apoptosis and it may be involved in cisplatin resistance in OSCC cells.

• 약학회지
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• 제43권3호
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• pp.385-390
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• 1999

Camptothecin (CPT) has been known to induce apoptosis in various cancer cell lines. To examine the intracellular apoptotic death signal initiated by CPT, we investigated the possible connection between caspase-3 activation and GSH depletion during CPT-induced apoptosis in HL-60 cells. Treatment of cells with $1{\;}{\mu}M$ CPT induced PARP cleavage accompanied by DNA fragmentation. z-VAD-fmk, a caspase-3 inhibitor, blocked the CPT-induced DNA fragmentation. Pretreatment of cells with N-acetylcysteine, a precursor of GSH biosynthesis, failed to inhibit CPT-induced PARP celavage and DNA gragmenatation. No significant changes in GSH depletion is not essential for caspase activation during CPT-induced apoptosis. We also investigated whether CPT-induced apoptosis is associated with changes of the levels of Bax and Bcl-2, two proteins involved in the control of apoptosis. Bcl-2 levels exhibited a late decrease compared with the kinetics of DNA fragmentation, whereas Bax levels increased more rapidly after CPT treatment. These results suggest that Bax plays more important role than Bcl-2 in inducing DNA fragmentation and may function upsteam of proteolytic activation of caspase-3 pathway in CPT-induced apoptosis.

• Biomolecules & Therapeutics
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• 제22권6호
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• pp.503-509
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• 2014

Paraquat has been suggested to induce apoptosis by generation of reactive oxygen species (ROS). However, little is known about the mechanism of paraquat-induced apoptosis. Here, we demonstrate that extracellular signal-regulated protein kinase (ERK) is required for paraquat-induced apoptosis in NIH3T3 cells. Paraquat treatment resulted in activation of ERK, and U0126, inhibitors of the MEK/ERK signaling pathway, prevented apoptosis. Moreover, paraquat-induced apoptosis was associated with cytochrome C release, which could be prevented by treatment with the MEK inhibitors. Taken together, our findings suggest that ERK activation plays an active role in mediating paraquat-induced apoptosis of NIH3T3 cells.