Researchers from Würzburg and Toyama have discovered that a compound isolated from tropical rainforest vines inhibits the growth of pancreatic cancer cells in the lab.
Professor Gerhard Bringmann, an expert in natural product chemistry, and his team from the Institute of Organic Chemistry at the Julius-Maximilians-Universität Würzburg (JMU) in Germany, together with Professor Suresh Awale and colleagues from the Institute of Natural Medicine of the University of Toyama in Japan have discovered a new, highly effective compound, which is a promising starting point to develop new drugs to treat pancreatic cancer.
A paper recently published in the Journal of Natural Products describes these exciting studies. The prestigious web portal "ACS News Service Weekly PressPac" of the American Chemical Society (ACS) now also presents the new findings to a broader public in a press release of 14 November 2018.
Cancer cells survive by activating the Akt/mTOR signalling pathway
Pancreatic cancer is one of the deadliest forms of cancer, with a five-year survival rate of less than five percent. Because these cancer cells proliferate so aggressively, they deplete nutrients and oxygen in the region of the tumor. Whereas most cells would die under such extreme conditions, pancreatic cancer cells survive by activating a cell signalling pathway called Akt/mTOR.
Some researchers are therefore looking for compounds with antiausterity properties that disrupt this pathway. Substances that are preferably toxic to cancer cells under nutrient deprived conditions are called antiausterity compounds deriving from the Greek word "austērótēs".
Alkaloids from rainforest vines
Suresh Awale, Gerhard Bringmann, and their teams previously identified some unusual alkaloids (naturally occurring organic compounds that contain nitrogen) with antiausterity potential from vines found in the Congolese rainforest.
Now the researchers from Würzburg and Japan have isolated and characterized the structure of ancistrolikokine E3 from twigs of the vine Ancistrocladus likoko, thereby identifying another promising new agent, which effectively targets PANC-1 pancreatic cancer cells in the lab.
Dramatic changes to the cancer cells
Ancistrolikokine E3 causes dramatic changes to the morphology of the cancer cells (see upper right illustration), which ultimately kill them. Furthermore, the compound inhibited cancer cell migration and colonization (see lower left illustration) in lab tests, which suggests that the compound could help prevent metastasis formation in patients.
The researchers showed that the compound kills the cancer cells by inhibiting the Akt/mTOR pathway and the autophagy pathway. The studies thus support that ancistrolikokine E3 and other structurally related alkaloids could be promising compounds for anticancer drug development based on the antiausterity strategy.
The work was funded by the German Research Foundation (DFG), the Japanese Society for the Promotion of Science (JSPS), the Excellence Scholarship Program BEBUC, and the German Academic Exchange Service (DAAD).
Prof. Dr. Suresh Awale, Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, T +81 76-434-760, suresh@inm.u.-toyama.ac.jp
Prof. Dr. Gerhard Bringmann, Institute of Organic Chemistry of the University of Würzburg, T +49 931-318-5323, bringman@chemie.uni-wuerzburg.de
"Ancistrolikokine E3, a 5,8‘-Coupled Naphthylisoquinoline Alkaloid, Eliminates the Tolerance of Cancer Cells to Nutrition Starvation by Inhibition of the Akt/mTOR/Autophagy Signaling Pathway". Journal of Natural Products 2018, 81, 2282-2291, doi: 10.1021/acs.jnatprod.8b00733
https://www.acs.org/content/acs/en/pressroom/presspacs/2018/acs-presspac-novembe... ACS PressPac
Robert Emmerich | Julius-Maximilians-Universität Würzburg
Further reports about: > CANCER > Cells > Julius-Maximilians-Universität > Vine > alkaloids > cancer cells > mTOR > pancreatic cancer > pancreatic cancer cells > signalling pathway
The impact of molecular rotation on a peculiar isotope effect on water hydrogen bonds
03.12.2019 | National Institutes of Natural Sciences
New treatment for brain tumors uses electrospun fiber
03.12.2019 | University of Cincinnati
With ultracold chemistry, researchers get a first look at exactly what happens during a chemical reaction
The coldest chemical reaction in the known universe took place in what appears to be a chaotic mess of lasers. The appearance deceives: Deep within that...
Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, the team of Dr. Yuval Rinkevich, Group Leader for Regenerative Biology at the Institute of Lung Biology and Disease at Helmholtz Zentrum München, aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene - a lineage not only present in skin, but also in fascia - the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.
Fibroblasts kit - ready to heal wounds
Research from a leading international expert on the health of the Great Lakes suggests that the growing intensity and scale of pollution from plastics poses serious risks to human health and will continue to have profound consequences on the ecosystem.
In an article published this month in the Journal of Waste Resources and Recycling, Gail Krantzberg, a professor in the Booth School of Engineering Practice...
Conventional light microscopes cannot distinguish structures when they are separated by a distance smaller than, roughly, the wavelength of light. Superresolution microscopy, developed since the 1980s, lifts this limitation, using fluorescent moieties. Scientists at the Max Planck Institute for Polymer Research have now discovered that graphene nano-molecules can be used to improve this microscopy technique. These graphene nano-molecules offer a number of substantial advantages over the materials previously used, making superresolution microscopy even more versatile.
Microscopy is an important investigation method, in physics, biology, medicine, and many other sciences. However, it has one disadvantage: its resolution is...
Anzeige
Anzeige
03.12.2019 | Event News
First International Conference on Agrophotovoltaics in August 2020
15.11.2019 | Event News
Laser Symposium on Electromobility in Aachen: trends for the mobility revolution
15.11.2019 | Event News
The impact of molecular rotation on a peculiar isotope effect on water hydrogen bonds
03.12.2019 | Life Sciences
SLAC scientists invent a way to see attosecond electron motions with an X-ray laser
03.12.2019 | Materials Sciences
Focused ultrasound may open door to Alzheimer's treatment
03.12.2019 | Medical Engineering