A high-throughput assay for screening natural products that boost NK cell-mediated killing of cancer cells

Autor: Zihang Xu, Xiaowen Zhu, Lin Su, Chunpu Zou, Xiao Chen, Yifei Hou, Chenyuan Gong, Wanyi Ng, Zhongya Ni, Lixin Wang, Xuewei Yan, Yangzhuangzhuang Zhu, Xiaoning Jiao, Chao Yao, Shiguo Zhu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Pharmaceutical Biology, Vol 58, Iss 1, Pp 357-366 (2020)
Druh dokumentu: article
ISSN: 1388-0209
1744-5116
13880209
DOI: 10.1080/13880209.2020.1748661
Popis: Context Natural killer (NK) cells can eliminate malignant cells and play a vital role in immunosurveillance. Administration of natural compounds represents a promising approach for antitumor immunotherapy, which may enhance the NK cell activity via multiple mechanisms. Objective Establishing approaches to evaluate the effect of select natural products on NK cell-mediated cytotoxicity. Materials and methods We selected a natural product library containing 2880 pure compounds, which was provided by the National Centre for Drug Screening of China. 0.1% DMSO was employed as a negative control, and 100 U/mL human recombinant IL-2 was employed as a positive control. To evaluate the % of tumour cells which were killed by NK cells, expanded NK cells were co-cultured with tumour cells and then treated with natural products at the concentration of 10 μM. After 24-h co-incubation, luminescent signal was detected and percent lysis was calculated. Results We report on the results of a three-round high-throughput screening effort that identified 20-deoxyingenol 3-angelate (DI3A) and its analogue ingenol 3-angelate (I3A) as immuno enhancers which boosts NK cell-mediated killing of non-small cell lung cancer cells (NSCLCs). Biophotonic cytotoxicity assay and calcein release assay were used as two well-established NK cell cytotoxicity detection assays to validate the immuno-enhancing effects of DI3A and I3A, which was achieved by increasing degranulation and interferon-gamma secretion of NK cells. Conclusions Our newly established ATP-based method was a valuable and information-rich screening tool to investigate the biological effects of natural products on both NK cells and tumour cells.
Databáze: Directory of Open Access Journals
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