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Multiple Molecular Targets of Sensitizers in Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL/Apo2L)-Mediated Apoptosis

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Author(s)
Kyoung-jin MinTaeg Kyu Kwon
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
생명과학회지
Issued Date
2011
Volume
21
Issue
11
Keyword
TRAILDeath receptorSensitizationCancer therapy
Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a recently identified member of the TNF ligand family that can initiate apoptosis through the activation of their death receptors. TRAIL has been paid attention as a potential anti-cancer drug because it selectively induces apoptosis in tumor cells in vitro and in vivo but not in most normal cells. However recent studies have shown that some cancer cells including malignant renal cell carcinoma and hepatocellular carcinoma are resistant to the apoptotic effects of TRAIL. Therefore single treatment with TRAIL may not be sufficient for the treatment of various malignant tumor cells. Understanding the molecular mechanisms of TRAIL resistance and identification of sensitizers capable of overcoming TRAIL resistance in cancer cells is needed for the establishment of more effective TRAIL-based cancer therapies. Chemotherapeutic drugs induce apoptosis and the upregulation of death receptors or activation of intracellular signaling pathways of TRAIL. Numerous chemotherapeutic drugs have been shown to sensitize tumor cells to TRAIL-mediated apoptosis. In this study we summarize biological agents and drugs that sensitize tumors to TRAIL-mediated apoptosis and discuss the potential molecular basis for their sensitization.
TNF ligand 군에 속하는 Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L)은 death receptor를 통한 세포사멸을 유도하는 것으로 알려졌다. TRAIL은 정상세포에서는 세포사를 일으키지 않고 암세포에서만 특이적으로 세포사멸을 유도함으로써 잠재력 있는 항암제로 주목을 받고 있다. 그러나 최근 연구에 의하면 악성 신장암과 간암과 같은 일부 암에서는 TRAIL에 의한 세포사에 저항성을 가지는 것으로 알려져 있다. 그러므로 TRAIL 만으로는 다양한 악성종양을 위한 치료법으로 적절하지 않다. TRAIL에 대한 저항성을 가지는 분자적 기전을 이해하고 TRAIL 저항성을 극복할 수 있는 증감제를 밝혀내는 것이 보다 효율적인 TRAIL을 이용한 암세포 치료 전략에 필요하다. 화학치료제들이 TRAIL 수용체인 death receptor의 발현을 증가시키고 세포 내의 TRAIL에 의한 신호전달 체계를 활성화 시키는 것으로 알려져 있고 이러한 기전을 통하여 다양한 화학치료제들이 TRAIL에 의한 세포사멸을 증가시키는 것을 확인하였다. 이 논문에서 우리는 TRAIL에 의한 세포사멸을 증가시키기 위한 생물학적 약물을 정리하고 그 분자적 기전을 고찰한다.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Kyoung-jin Min and Taeg Kyu Kwon. (2011). Multiple Molecular Targets of Sensitizers in Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL/Apo2L)-Mediated Apoptosis. 생명과학회지, 21(11), 1641–1651. doi: 10.5352/JLS.2011.21.11.1641
Type
Article
ISSN
1225-9918
DOI
10.5352/JLS.2011.21.11.1641
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/36522
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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