A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs

Ningning Tang; Ling Li; Fei Xie; Ying Lu; Zifan Zuo; Hao Shan; Quan Zhang; Lianwen Zhang

doi:10.1016/j.jpha.2021.04.001

Volume 11 Issue 6

Dec. 2021

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Article Navigation > Journal of Pharmaceutical Analysis > 2021 > 11(6): 808-814

Ningning Tang, Ling Li, Fei Xie, Ying Lu, Zifan Zuo, Hao Shan, Quan Zhang, Lianwen Zhang. A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs[J]. Journal of Pharmaceutical Analysis, 2021, 11(6): 808-814. doi: 10.1016/j.jpha.2021.04.001

Citation:

Ningning Tang, Ling Li, Fei Xie, Ying Lu, Zifan Zuo, Hao Shan, Quan Zhang, Lianwen Zhang. A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs[J]. Journal of Pharmaceutical Analysis, 2021, 11(6): 808-814. doi: 10.1016/j.jpha.2021.04.001

Citation:

Ningning Tang, Ling Li, Fei Xie, Ying Lu, Zifan Zuo, Hao Shan, Quan Zhang, Lianwen Zhang. A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs[J]. Journal of Pharmaceutical Analysis, 2021, 11(6): 808-814. doi: 10.1016/j.jpha.2021.04.001

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A living cell-based fluorescent reporter for high-throughput screening of anti-tumor drugs

doi: 10.1016/j.jpha.2021.04.001

a. College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, 300350, China;
b. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China

Funds:

We gratefully appreciate the financial support from the National Natural Science Foundation of China (Grant No.: 31470795), Tianjin Municipal Science and Technology Commission (Grant No.: 15JCYBJC24100), and the “Fundamental Research Funds for the Central Universities”, Nankai University (Grant No.: 63191148).

Received Date: Jul. 22, 2020
Accepted Date: Apr. 01, 2021
Rev Recd Date: Mar. 31, 2021
Available Online: Jan. 12, 2022
Publish Date: Dec. 15, 2021

Abstract

Abstract

Suppression of cellular O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) can repress proliferation and migration of various cancer cells, which opens a new avenue for cancer therapy. Based on the regulation of insulin gene transcription, we designed a cell-based fluorescent reporter capable of sensing cellular O-GlcNAcylation in HEK293T cells. The fluorescent reporter mainly consists of a reporter (green fluorescent protein (GFP)), an internal reference (red fluorescent protein), and an operator (neuronal differentiation 1), which serves as a “sweet switch” to control GFP expression in response to cellular O-GlcNAcylation changes. The fluorescent reporter can efficiently sense reduced levels of cellular O-GlcNAcylation in several cell lines. Using the fluorescent reporter, we screened 120 natural products and obtained one compound, sesamin, which could markedly inhibit protein O-GlcNAcylation in HeLa and human colorectal carcinoma-116 cells and repress their migration in vitro. Altogether, the present study demonstrated the development of a novel strategy for anti-tumor drug screening, as well as for conducting gene transcription studies.
- Fluorescent reporter,
- High-throughput screening,
- O-linked β-N-acetylglucosaminylation,
- Anti-tumor drug,
- Gene transcriptional regulation

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References(37)

References

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