ReferenceID 489

Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy

Autophagy

Targeting macroautophagy/autophagy is a novel strategy in cancer immunotherapy. In the present study, we showed that the natural product rocaglamide (RocA) enhanced natural killer (NK) cell-mediated lysis of non-small ce

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Reference Id
489
Evidence Id
17079
Core Evidence Id
17079
Source Reference Id
1146
Herb2 Reference Id
HBREF001932
Subject Paper Key
HBIN042379_29969944
Pubmed Id
29969944
Doi
10.1080/15548627.2018.1489946
Paper Title
Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy
Paper Abstract
Targeting macroautophagy/autophagy is a novel strategy in cancer immunotherapy. In the present study, we showed that the natural product rocaglamide (RocA) enhanced natural killer (NK) cell-mediated lysis of non-small cell lung cancer (NSCLC) cells in vitro and tumor regression in vivo. Moreover, this effect was not related to the NK cell recognition of target cells or expressions of death receptors. Instead, RocA inhibited autophagy and restored the level of NK cell-derived GZMB (granzyme B) in NSCLC cells, therefore increasing their susceptibility to NK cell-mediated killing. In addition, we further identified that the target of RocA was ULK1 (unc-51 like autophagy activating kinase 1) that is required for autophagy initiation. Using firefly luciferase containing the 5 untranslated region of ULK1, we found that RocA inhibited the protein translation of ULK1 in a sequence-specific manner. Taken together, RocA could block autophagic immune resistance to NK cell-mediated killing, and our data suggested that RocA was a promising therapeutic candidate in NK cell-based cancer immunotherapy.
Journal
Autophagy
Publish Year
2018
Experiment Subject
Experiment Type
Cell Experiment
Phenotype Related
Paper Title Cn
Paper Title En
Rocaglamide enhances NK cell-mediated killing of non-small cell lung cancer cells by inhibiting autophagy
Bilingual Status
semi_complete