Chinese scientists pioneered the cell metabolism fluorescent probe - SoNar

Release date: 2015-05-11

The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, and the Shanghai Biomanufacturing Technology Collaborative Innovation Center Yang Yu team pioneered a new type of fluorescent probe that monitors the metabolic state of single cells and living animals, and screened for a highly effective anticancer compound. , revealing its mechanism. On May 5, relevant research results were published in the journal Cell-Metabolism.

Metabolic changes in cancer cells are the root cause of tumorigenesis and growth; killing, inhibiting cancer cells, or returning them to normal cells by controlling abnormal metabolism of cancer cells can effectively inhibit the progression of cancer. However, using traditional biochemical analysis methods to study cellular metabolic activities and search for anticancer drugs, there are technical bottlenecks of low efficiency and high cost. NAD/NADH is a pair of core metabolites that are the best parameters for characterizing cellular metabolic imbalances.

The new cell metabolism fluorescent probe SoNar developed by Yang Wei team is based on synthetic biology method. It has high sensitivity, high brightness and great dynamic range. It can detect the difference of micro-metabolism between cancer cells and normal cells, realizing in single cells and living bodies. High temporal and spatial resolution detection and imaging of animal metabolic status at the animal level. Using SoNar, the team conducted a first-passage high-throughput compound screening based on cellular metabolism and found that compound KP372-1 can kill cancer cells of different human tissue types at low concentrations.

Using techniques such as metabolomics, chemical biology, and genetic screening, the researchers finally identified KP372-1 as a novel redox cycle substrate that is highly catalyzed by NQO1 enzymes that are specifically expressed in cancer cells. Oxidative stress, which in turn kills cancer cells. It is reported that this compound has higher oral availability, longer drug action half-life and lower pharmacodynamic concentration than the classic NQO1-dependent anticancer compound β-lapaquin which has entered clinical phase II.

It is reported that under the guidance of Yang Lan, the research work was completed by graduate students such as Zhao Yuzheng and Hu Qingxun in five years. At the same time, SoNar probes can be widely used for real-time monitoring of living cells and living cells related to cell metabolism, providing important innovative tools and means for people to better understand the regulation mechanism of substance and energy metabolism.

Source: Instrument Information Network

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