원문정보
초록
영어
DR5 and DR4, death receptors of TNF-related apoptosis-inducing ligand (TRAIL), are interesting targets of antibody-based therapy, since TRAIL itself selectively induces apoptotic cell death in cancer cells. In previous study we showed that a human single-chain variable fragment (scFv) antibody (HW1) against DR5 induces autophagic cell death. Recent studies show that despite the marked differences between apoptosis and autophagic cell death, their regulation is intimately connected and the same regulators can sometimes control both apoptosis and autophagy. We studied the mechanisms of crosstalk between TRAIL-induced apoptosis and HW1-induced autophagic cell death. 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). We will present molecular mechanisms of how the combination of poptosistriggering
TRAIL and autophagy-stimulating HW1 showed the synergistic cell death inducing activity.