(Press-News.org) A chemist from Purdue University has found a way to synthesize a compound to fight a previously "undruggable" cancer protein with benefits across a myriad of cancer types.
Inspired by a rare compound found in a shrub native to North America, Mingji Dai, professor of chemistry and a scientist at the Purdue University Center for Cancer Research, studied the compound and discovered a cost-effective and efficient way to synthesize it in the lab. The compound -- curcusone D -- has the potential to help combat a protein found in many cancers, including some forms of breast, brain, colorectal, prostate, lung and liver cancers, among others. The protein, dubbed BRAT1, had previously been deemed "undruggable" for its chemical properties. In collaboration with Alexander Adibekian's group at the Scripps Research Institute, they linked curcusone D to BRAT1 and validated curcusone D as the first BRAT1 inhibitor.
Curcusones are compounds that come from a shrub named Jatropha curcas, also called the purging nut. Native to the Americas, it has spread to other continents, including Africa and Asia. The plant has long been used for medicinal properties -- including the treatment of cancer -- as well as being a proposed inexpensive source of biodiesel.
Dai was interested in this family of compounds -- curcusone A, B, C and D.
"We were very interested by these compounds' novel structure," Dai said. "We were intrigued by their biological function; they showed quite potent anti-cancer activity and may lead to new mechanisms to combat cancer."
Researchers tested the compounds on breast cancer cells and found curcusone D to be extremely effective at shutting down cancer cells. The protein they were targeting, BRAT1, regulates DNA damage response and DNA repair in cancer cells. Cancer cells grow very fast and make a lot of DNA. If scientists can damage cancer cells' DNA and keep them from repairing it, they can stop cancer cells from growing.
"Our compound can not only kill these cancer cells, it can stop their migration," Dai said. "If we can keep the cancer from metastasizing, the patient can live longer."
Stopping cancer from spreading throughout the body -- metastasizing -- is key to preserving a cancer patient's life. Once cancer starts to migrate from its original organ into different body systems, new symptoms start to develop, often threatening the patient's life.
"For killing cancer cells and stopping migration, there are other compounds that do that," Dai said. "But as far as inhibiting the BRAT1 protein, there are no other compounds that can do that."
Dai and his team believe that as effective as curcusone D is by itself, it may be even more potent as part of a combination therapy. They tested it alongside a DNA damaging agent that has already been approved by the Food and Drug Administration and found that this combination therapy is much more effective.
One difficulty in studying curcusones as potential cancer treatments is that, while the shrub they come from is common and inexpensive, it takes massive amounts of the shrub to yield even a small amount of the compounds. Even then, it is difficult to separate the compounds they were interested in from the rest of the chemicals in the shrub's roots.
"In nature, the plant doesn't produce a lot of this compound," Dai said. "You would need maybe as much as 100 pounds of the plant's dry roots to get just about a quarter teaspoon of the substance -- a 0.002% yield."
That small yield is relevant for production, because if it is effective as a cancer treatment, pharmacists will need a lot more of it. Additionally, having an abundant supply of the compounds makes studying them easier, quicker and less expensive.
"That's why a new synthesis is so important," Dai said. "We can use the synthesis to produce more compounds in a purer form for biological study, allowing us to advance the field. From there, we can make analogs of the compound to improve its potency and decrease the potential for side effects."
The next step will be to test the compound to ensure that it is not toxic to humans, something the researchers are optimistic about since the shrub it came from has been used as a traditional medicine in a number of cultures. Already, researchers from other entities have reached out to test the compound on the cancers they study, bringing hope for renewed therapeutics for treating the disease.
"Many of our most successful cancer drugs have come from nature," Dai said. "A lot of the low-hanging fruit, the compounds that are easy to isolate or synthesize, have already been screened and picked over. We are looking for things no one has thought about before. Once we have the chemistry, we can build the molecules we're interested in and study their biological function."
INFORMATION:
This research was funded through grants from the National Institutes of Health and the National Science Foundation. Patent application U.S. 63/084,594 covers this finding.
About Purdue University Center for Cancer Research
At the Purdue University Center for Cancer Research, our mission is basic discovery -- discovery that is the foundation for innovative cancer solutions. PCCR leverages Purdue's strengths in engineering, veterinary medicine, nutrition science, chemistry, medicinal chemistry, pharmacy, structural biology and biological sciences to establish its foundational base. As a National Cancer Institute-designated cancer center, PCCR is making significant contributions to emerging technologies, such as cancer vaccines and combination chemotherapy. We specialize in translational research that saves lives by translating laboratory findings into new and innovative therapies as quickly as possible. Our mission is discovery. Our goal is to cure cancer.
About Purdue University
Purdue University is a top public research institution developing practical solutions to today's toughest challenges. Ranked the No. 5 Most Innovative University in the United States by U.S. News & World Report, Purdue delivers world-changing research and out-of-this-world discovery. Committed to hands-on and online, real-world learning, Purdue offers a transformative education to all. Committed to affordability and accessibility, Purdue has frozen tuition and most fees at 2012-13 levels, enabling more students than ever to graduate debt-free. See how Purdue never stops in the persistent pursuit of the next giant leap at https://purdue.edu/.
Astronauts who spend extended time in space face stressors such as isolation, confinement, lack of privacy, altered light-dark cycles, monotony and separation from family. Interestingly, so do people who work at international research stations in Antarctica, where the extreme environment is characterized by numerous stressors that mirror those present during long-duration space exploration.
To better understand the psychological hurdles faced by astronauts, University of Houston professor of psychology Candice Alfano and her team developed the Mental Health Checklist (MHCL), a self-reporting instrument for detecting ...
A Texas A&M researcher is discovering the demographic characteristics that can produce or lessen stress for racial and ethnic minority students in school settings.
The study, recently published in the journal Ethnicity and Disease, collected mental health survey assessments among 389 sixth-graders from 14 Texas public schools in urban areas. Melissa DuPont-Reyes, assistant professor at the Texas A&M University School of Public Health, led the investigation of self-reported depressive-anxious symptoms over a two-year period. This issue of the journal highlighted research by early stage investigators, especially scholars of color, to advance new knowledge ...
A mollusk and shrimp are two unlikely marine animals that are playing a very important role in engineering. The bodies of both animals illustrate how natural features, like the structures of their bones and shells, can be borrowed to enhance the performance of engineered structures and materials, like bridges and airplanes. This phenomenon, known as biomimetics, is helping advance structural topology research, where the microscale features found in natural systems are being mimicked.
In a recent paper published by researchers at the Georgia Institute of Technology and the Pontifical Catholic University of Rio de ...
WASHINGTON, April 20, 2021 -- Fiber optic technology is the holy grail of high-speed, long-distance telecommunications. Still, with the continuing exponential growth of internet traffic, researchers are warning of a capacity crunch.
In AVS Quantum Science, by AIP Publishing, researchers from the National Institute of Standards and Technology and the University of Maryland show how quantum-enhanced receivers could play a critical role in addressing this challenge.
The scientists developed a method to enhance receivers based on quantum physics properties to dramatically increase network ...
Researchers at Johannes Gutenberg University Mainz (JGU) in Germany and the Institute of Molecular Biology of Barcelona in Spain have discovered how the blood plasma protein fetuin-B binds to the enzyme meprin β and used a computer model to visualize their findings. These results could lead to the development of new drugs to treat serious diseases such as Alzheimer's and cancer. Meprin β releases proteins from cell membranes, thus controlling important physiological functions in the human body. However, a dysregulation of this process can trigger the development of Alzheimer's and ...
Earthquake early warnings can be delivered successfully using a small network of off-the-shelf smartphones attached to building baseboards, according to a study conducted in Costa Rica last year.
In his presentation at the Seismological Society of America (SSA)'s 2021 Annual Meeting, Ben Brooks of the U.S. Geological Survey said the ASTUTI (Alerta Sismica Temprana Utilizando Teléfonos Inteligentes) network of more than 80 stations performed comparably to scientific-grade warning systems.
During six months' of ASTUTI operation, there were 13 earthquakes that caused noticeable ...
The famous 1700 Cascadia earthquake that altered the coastline of western North America and sent a tsunami across the Pacific Ocean to Japan may have been one of a sequence of earthquakes, according to new research presented at the Seismological Society of America (SSA)'s 2021 Annual Meeting.
Evidence from coastlines, tree rings and historical documents confirm that there was a massive earthquake in the U.S. Cascadia Subduction Zone on 26 January 1700. The prevailing hypothesis is that one megathrust earthquake, estimated at magnitude 8.7 to 9.2 and involving the entire tectonic plate boundary in the region, was responsible ...
When hydraulic fracturing operations ground to a halt last spring in the Kiskatinaw area of British Columbia, researchers expected seismic quiescence in the region. Instead, hundreds of small earthquakes occurred for months after operations shut down, according to a new study.
In her presentation at the Seismological Society of America (SSA)'s 2021 Annual Meeting, Rebecca Salvage of the University of Calgary said about 65% of these events could not be attributed to either natural seismicity or active fluid injection from hydraulic fracturing operations.
Salvage and her colleagues instead suggest the latent earthquakes may be the result of aseismic slip, driven by fluid from previous hydraulic fracture injections keeping rock pore pressures elevated.
"Because there are lots of faults ...
BOSTON - New research from Boston Medical Center identifies elevated mortality risk for women with back pain when compared to women without back pain. Back pain was not associated with mortality among men indicating long-term consequences of back pain may differ by sex. The overall findings suggest that mild back pain (pain that does not keep a person from exercising or doing daily activities) is unlikely to impact the length of one's life, but risk of mortality was increased among adults with more severe back pain. Published in the Journal of General Internal Medicine, this new study raises ...
The lack of accountability, poor communication and insufficient planning plaguing the government’s response to the COVID-19 pandemic -- especially in its early months -- have roots in how the nation responded to 9/11, Hurricane Katrina and the H1N1 swine flu, a new study involving the University of Washington found.
Focusing on the way government agencies assemble and allocate resources - the procurement system - researchers said the successes and shortcomings of responses to other large-scale crises show that a more centralized approach can achieve goals faster and more effectively.
"In the moment of disasters, we prioritize saving ...
