Molecular probes that can illuminate cancer cells are often invaluable tools in the fight against the disease. The latest addition to this group is a family of fluorescent probes that can highlight a particularly pernicious kind of tumor cell: those resistant to anticancer drugs.
Figure 1: Fluorescent probes light up living cancer cells to indicate the presence of glutathione transferase (GST), an enzyme associated with drug resistance. Copyright : 2011 American Chemical Society
The international team of scientists behind the research, led by Hiroshi Abe at the RIKEN Advanced Science Institute in Wako, Japan, and Ralf Morgenstern at the Karolinska Institute in Stockholm, Sweden, say that their discovery could help expedite research efforts to defeat these drug-resistant tumors1.
The probes work by targeting a family of enzymes called glutathione transferases (GSTs). These enzymes play a variety of roles in healthy cells, including protecting the cell from oxidative stress by labeling harmful molecules with a glutathione tag. This tag marks the molecule for rapid export out of the cell. But in certain cancer cells, GSTs are produced in elevated amounts, where they are able to tag many anticancer drugs in the same way. As a result, the drug is pumped away before it can kill the cell. Finding ways to block GSTs is therefore an active area of cancer research since a probe that can reveal the level of GST activity inside a living cell could prove a very useful tool in the search.
The team’s fluorescent probes exploit the GSTs well-known molecular mode of action. The GST enzymes target molecules—such as anti-cancer drugs—by attacking an electron-poor point in its structure and attaching the glutathione label to it. Using a series of known fluorescent molecules, Abe, Morgenstern and colleagues added to them an electron-poor arylsulfonyl group ripe for attack by a GST enzyme. The arylsulfonyl group also has the effect of suppressing the fluorescence; but, as GST attacks, it breaks the probe in two which releases the fluorophore and instantly illuminates the cell.
The researchers demonstrated that they could use their probes to quantitatively measure very low levels of GST in cell extracts. Using a fluorophore known as cresyl violet, they were also able to image GST activity inside living cells (Fig. 1). According to Abe, the researchers already have plans to improve the performance of their probes, making them even more sensitive.
“By fine-tuning the chemical reactivity of the protecting arylsulfonyl group, we will improve the signal to background noise ratio for improved imaging,” he says. “By re-designing the fluorescent compound, we can also achieve GST subtype selectivity,” he adds.
The corresponding author for this highlight is based at the Nano Medical Engineering Laboratory, RIKEN Advanced Science Institute
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
26.04.2017 | Materials Sciences
26.04.2017 | Agricultural and Forestry Science
26.04.2017 | Physics and Astronomy