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

Autor: Shiguo Zhu, Wanyi Ng, Chenyuan Gong, Chunpu Zou, Xuewei Yan, Xiaoning Jiao, Zihang Xu, Lixin Wang, Chao Yao, Xiao Chen, Yangzhuangzhuang Zhu, Yifei Hou, Zhongya Ni, Lin Su, Xiaowen Zhu
Rok vydání: 2020
Předmět:
Cell Survival
Cytotoxicity
20-deoxyingenol 3-angelate
Pharmaceutical Science
chemical and pharmacologic phenomena
Context (language use)
RM1-950
Biology
030226 pharmacology & pharmacy
01 natural sciences
03 medical and health sciences
0302 clinical medicine
Ingenol 3-angelate
Cell Line
Tumor
Drug Discovery
Humans
Malignant cells
non-small cell lung cancer
Pharmacology
Biological Products
Dose-Response Relationship
Drug
food and beverages
General Medicine
ingenol 3-angelate
Coculture Techniques
Cell mediated immunity
High-Throughput Screening Assays
0104 chemical sciences
Killer Cells
Natural
Immunosurveillance
010404 medicinal & biomolecular chemistry
Complementary and alternative medicine
Cancer cell
Leukocytes
Mononuclear
Cancer research
Interleukin-2
Molecular Medicine
Therapeutics. Pharmacology
Research Article
Zdroj: Pharmaceutical Biology
Pharmaceutical Biology, Vol 58, Iss 1, Pp 357-366 (2020)
ISSN: 1744-5116
1388-0209
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: OpenAIRE
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