Cancer cells typically avoid death by hijacking molecular chaperones that guide and protect the proteins that ensure normal cellular function and then tricking them into helping mutated versions of those proteins stay alive, says Dr. Ahmed Chadli, a researcher in the Molecular Chaperone Program at the GRU Cancer Center and senior author of the study named the Journal of Biological Chemistry's Paper of the Week.
Drug development has focused on the chaperone Hsp90 (heat shock protein 90) because it plays a key role in assisting mutated proteins, making it an attractive cancer drug target. However, the clinical efficacy of Hsp90 inhibitors has been disappointing. Most current small molecules targeting Hsp90 have inadvertently resulted in the expression of proteins that protect cancer cells from programmed cell death and compromise the Hsp90 inhibitors in the clinic.
In this study, however, Chaitanya Patwardhan, a graduate student in Dr. Chadli's lab, found that gedunin, an Indian plant compound, attacks a co-chaperone, or helper protein, of Hsp90 called p23.
"This compound binds directly to p23, leading to inactivation of the Hsp90 machine—without production of anti-apoptotic proteins—thus killing cancer cells," said Dr. Chadli. "The idea here is that this will open a door for new ways of targeting Hsp90 by targeting its helper proteins, which may be used in combination with established Hsp90 inhibitors that are ongoing clinical trials. In the future, this research could have applications in drug development for hormone-dependent cancers, including breast, prostate and endometrial cancers."
"One of the major areas of scientific emphasis of the GRU Cancer Center is to develop therapeutic approaches to cancer targeting specific molecules within the cancer cell, including chaperones," said Dr. Samir N. Khleif, Director of the GRU Cancer Center. "This finding is an important piece of the puzzle, bringing us closer to our goal of helping patients with cancer."
Along with Patwardhan, the study was also authored by Dr. Abdul Fauq, Mayo Clinic College of Medicine; Laura B. Peterson and Dr. Brian S.J. Blagg, both of the University of Kansas; and Dr. Charles Miller, Tulane University School of Public Health and Tropical Medicine.
Dr. Chadli's lab is also the recipient of a National Institutes of Health R01 grant to look for new molecules targeting the Hsp90 machine.
Only the top 2 percent of the 6,600 manuscripts annually reviewed in terms of significance and overall importance, by the JBC are ranked as Papers of the Week. The study will also be the focus of an upcoming JBC podcast.
Danielle Moores | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
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...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences