• 생명과학회지
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• 제22권5호
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• pp.697-701
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• 2012

본 연구에서는 항응고제로서의 역할을 가지면서 또한 혈액응고와는 관련 없는 종양세포의 전이 등을 조절하는 것으로 알려진 activated protein C (APC)가 종양세포의 사멸에는 어떠한 영향을 미치는 지에 대한 연구를 수행하였다. Tumor necrosis factor (TNF)-${\alpha}$와 cyclohexamide를 병합 처리하거나 FAS를 처리하게 되면 인간 신장암세포인 Caki에서는 유의적인 세포사멸이 일어난다. 하지만, APC는 이러한 세포사멸에 아무런 영향을 미치지 못하였다. 또한 TRAIL을 인간 뇌 암세포인 T98G와 유방암세포인 MDA231세포에 처리하여 세포사멸을 일으켰을 때에도 APC는 세포사멸을 조절하지 못하였다. 그러나, TRAIL에 대한 민감도를 증가시키기 위한 kahweol과 TRAIL의 병합처리나, kahweol과 malatonin의 병합처리에 의한 신장암세포의 사멸은 APC에 의해 유의적으로 억제되는 것을 확인하였다. 따라서, 이는 APC가 항암치료의 효율성을 조절 할 수 있는 가능성을 가짐을 의미한다.

• 생명과학회지
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• 제21권7호
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• pp.953-960
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• 2011

세포괴사는 세포막의 파열, HMGB1을 포함한 세포 내용물의 세포외부로의 방출 등을 수반하는 세포죽음이다. HMGB1은 핵 단백질로 전사조절자로 작용하지만 세포괴사에 의해 세포 밖으로 방출되면 염증을 유발하고 암을 촉진하는 cytokine으로 작용한다. HMGB1의 과발현은 암 발생 및 항암제 저항과 밀접한 연관성을 가지고 있지만, 그 기작에 대한 연구는 미흡한 실정이다. 본 연구에서는, HMGB1이 항암제에 의한 세포 죽음에 미치는 영향을 조사하였다. 그 결과, HMGB1은 MCF-7, MDA-MB231, MDA-MB361 세포에서 cisplatin에 의한 세포사멸을 억제하고 세포운명을 세포괴사로 바꾼다는 사실을 확인하였다. HMGB1의 세포사멸-세포괴사 전환 작용을 4-HC를 처리한 세포에서도 관찰되었다. 그러나, HMGB1은 docetaxel (DOC)에 의한 세포사멸에는 영향을 주지 않음을 확인하였다. MTS를 이용하여 항암제에 의한 세포 죽음에 미치는 영향을 조사한 결과, necrotic core가 형성된 8일째 MCF-7 MTS에서 cisplatin에 의한 세포사멸이 세포괴사로 바뀌는 반면, DOC에 의한 세포사멸은 세포괴사로 전환되지 않는 것을 확인하였다. 또한 spheroid에서 HMGB1 receptor인 RAGE의 발현이 증가함을 확인하였다. 이러한 결과를 통해, HMGB1이 alkylating agent에 의한 세포사멸을 세포괴사로 전환시킴을 알 수 있었다. 따라서, alkylating agent에 의한 항암제 효능을 나타내기 위해선, 이들 항암제의 부작용 즉 세포괴사를 억제하는 전략이 필요한 것으로 생각된다.

• BMB Reports
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• 제51권5호
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• pp.219-224
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• 2018

Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

• BMB Reports
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• 제31권2호
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• pp.183-188
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• 1998

2-chloroethylethyl sulfide (CEES) is an alkylating agent that readily reacts with a wide variety of biological molecules causing metabolic abnormality. The mechanism of cell death during CEES injury is poorly understood. We have examined the effect of exposure of thymocytes with various concentrations of CEES to determine the pattern of cell death in thymocytes injury induced by CEES. In the present study, we show that two patterns of cell death occurred by either one of two mechanisms: apoptosis and necrosis. Exposure to low level of CEES (100 ${\mu}M$) for 5 h caused an induction of apoptosis on thymocytes, as identified by the following criteria: DNA fragmentation visualized by the characteristic "ladder" pattern was observed upon agarose gel electrophoresis and morphological features were revealed by microscopical observations. In contrast, exposure to high levels of CEES (500 ${\mu}M$) induce necrotic features such as cell lysis. Thus, depending on the concentrations, CEES can result in either apoptotic or necrotic cell damage. Our findings suggest that thymocytes which are not killed directly, but merely injured by low levels of CEES, are able to activate an internally-programmed cell death mechanism, whereas thymocytes receiving severe damages apparently can not.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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• pp.43-50
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• 2002

• Applied Microscopy
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• 제26권3호
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• pp.369-377
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• 1996

Ultrastructural changes of chloride cells in the gill from seawater-adapted killifish (Orizias latipes) were studied with a transmission electronmicroscope. Chloride cells contain many mitochondria and specifically developed tubular systems. Apical pits, formed by several neighboring chloride cells, were exposed to the environment. Degeneration and death of the chloride cells by apoptosis occurred more frequently than by necrosis. Apoptotic chloride cells shrank, became to apoptotic bodies, and eventually were phagocytosed and digested by the microphages around them. We conclude that apoptosis plays an important role in increased cellular turnover of chloride cells for the osmoregulation caused by changes in salinity of the environment.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8533-8539
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• 2016

Background: B-cell chronic lymphocytic leukemia B (B-CLL), the most common type of leukemia, may be caused by apoptosis deficiency in the body. Adipose tissue-derived mesenchymal stem cells (AD-MSCs) as providers of pro-apoptotic molecules such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), can be considered as an effective anti-cancer therapy candidate. Therefore, in this study we assessed the role of tumor necrosis factor-producing mesenchymal stem cells oin apoptosis of B-CLL cells resistant to fludarabine-based chemotherapy. Materials and Methods: In this study, after isolation and culture of AD-MSCs, a lentiviral LeGO-iG2-TRAIL-GFP vector containing a gene producing the ligand pro-apoptotic with plasmid PsPAX2 and PMDG2 virus were transfected into cell-lines to generate T293HEK. Then, T293HEK cell supernatant containing the virus produced after 48 and 72 hours was collected, and these viruses were transduced to reprogram AD-MSCs. Apoptosis rates were separately studied in four groups: group 1, AD-MSCs-TRAIL; group 2, AD-MSCs-GFP; group 3, AD-MSCs; and group 4, CLL. Results: Observed apoptosis rates were: group 1, $42{\pm}1.04%$; group 2, $21{\pm}0.57%$; group 3, $19{\pm}2.6%$; and group 4, % $0.01{\pm}0.01$. The highest rate of apoptosis thus occurred ingroup 1 (transduced TRAIL encoding vector). In this group, the average medium-soluble TRAIL was 72.7pg/m and flow cytometry analysis showed a pro-apoptosis rate of $63{\pm}1.6%$, which was again higher than in other groups. Conclusions: In this study we have shown that tumor necrosis factor (TNF) secreted by AD-MSCs may play an effective role in inducing B-CLL cell apoptosis.

• Advances in Traditional Medicine
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• 제9권1호
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• pp.67-73
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• 2009

Temporary clamping of the portal triad is a common strategy to minimize bleeding during liver transplantation. Increasing evidences suggests that oxygen derived free radicals and reintroduction of oxygen in ischemic tissue lead to ischemic and reperfusion injury (I/R) and lead to apoptosis and necrosis. Adult Wistar rat subjected to 60 min of partial liver ischemia followed by three hour reperfusion. Eighteen Wister rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion group (II) (n = 6), folic acid treated group (1 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n = 6). Apoptotic and necrotic hepatocytes, mitochondrial antioxidant enzymes were measured. Liver injury was assessed by alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology and electron microscopy. An ischemic and reperfusion hepatocellular injury was indicated by increased serum-ALT, AST, histopathology and electron microscopy studies. Apoptotic and necrotic cells were increased which was revealed by flow cytometry in I/R group. Pre- treatment with folic acid significantly decreased serum -ALT, AST levels, apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Histopathology and TEM studies showed markedly diminished hepatocellular injury in folic acid pretreated rats during the hepatic I/R, which reached a level comparable to saline-treated rat of sham operated group. On the basis of our findings it may be concluded that folic acid afforded significant protection from necrosis and apoptosis in I/R injury.

• Advances in Traditional Medicine
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• 제3권3호
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• pp.151-156
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• 2003

The leaves of Mirabilis jalapa L contains protein fraction presumed ribosome-inactivating protein (RIP). RIP is a group of protein that has RNA N-glycosidase activity that is capable to inhibit protein synthesis. Protein fraction of the plant was shown to be cytotoxic on HeLa cell-line, however, the mechanism by which the protein kill the cells is not identified yet, whether trough apoptosis, necrosis, or other mechanism. This research aim to study the mechanism of cell death caused by the protein fraction isolated from the leaves of this plant on HeLa and Raji cell-line, as representative of different kind of cancer cells. Results showed that protein fraction isolated from the leaves of Mirabilis jalapa L was more cytotoxic to HeLa cell-line (LC50: 0.65 mg/ml) than to Raji cell-line (1.815 mg/ml) on 48 hours incubation time. Moreover, it was demonstrated that the death of HeLa cells caused by the protein fraction was due to induction of apoptosis, while on Raji cell-line was due to non-apoptosis way, presumably via necrosis.

• BMB Reports
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• 제41권1호
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• pp.1-10
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• 2008

Surgery, Chung-Ang Unviersity College of Medicine, Yong-San Hospital, Seoul, Korea Apoptosis is considered to be a programmed and controlled mode of cell death, whereas necrosis has long been described as uncontrolled and accidental cell death resulting from extremely harsh conditions. In the following review, we will discuss the features and physiological meanings as well as recent advances in the elucidation of the signaling pathways of both apoptotic cell death and programmed necrotic cell death.