Synergic Effect on Cell Death by Co-treatment with TRAIL and Human Anti-DR5 Antibody

DR5 and DR4, death receptors of TNF-related apoptosis-inducing ligand (TRAIL), are interesting targets of antibody-based cancer therapy since TRAIL itself selectively induces apoptotic cell death in cancer cells but not in normal cells. In previous study we isolated a human single-chain variable fragment (scFv) antibody (HW1) that recognizes a different epitope on DR5 form that of TRAIL and induced autophagic cell death. when treated to various cancer cell lines. To study the interaction between TRAIL-induced apoptosis and HW1-induced autophagic cell death delivered from DR5 receptor, we analyze cytotoxicity, cell death type, and signaling molecules in HCT116 cells treated with TRAIL, HW1 and combination of them. Our results showed that the co-treatment of TRAIL and HW1 significantly enhanced cytotoxic effect on HCT116 compared with each single treatment. Transmission electron microscopy analysis showed that the cells were dying with both apoptotic (blebbing and DNA fragmentation) and autophagic features (autophagosome containing organelles). Analyses of each signaling markers (apoptosis; PARP cleavage and autophagy; increased LC3-II form) induced by TRAIL, HW1 and combination of them showed that the combination of TRAIL and HW1 elevates each marker's level compared with single agents. Studies for the interplay between regulators related to apoptotic and autophagic cell death pathway should be followed at molecular levels. Our findings would provide a promising and novel strategy involving synergistic contribution of apoptotic and autophagic signaling through DR5 to the cell death of cancer cells.

Author dc:creator

• 김, 태인

Contributors dc:contributor

• 권, 명희
• 대학원 의학과
• 200624168

• 아팝토시스
• 오토파지
• 상승효과

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000009235
000000009235

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1819