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Rocaglamide Enhances NK Cell-Mediated Killing of Non-Small Cell Lung Cancer Cells by Inhibiting Autophagy

Rocaglamide Enhances NK Cell-Mediated Killing of Non-Small Cell Lung Cancer Cells by Inhibiting Autophagy

Chao Yao, Zhongya Ni, Chenyuan Gong, Xiaowen Zhu, Lixin Wang, Zihang Xu, Chunxian Zhou, Suyun Li, Wuxiong Zhou, Chunpu Zou, Shiguo Zhu

Autophagy. 2018;14(10):1831-1844.

PMID: 29969944

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP84573160	Rocaglamide		84573-16-0	Price

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