Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Obesity drug inhibits prostate tumor growth


Proteomics screen identifies novel prostate cancer target

The Burnham Institute’s Jeffrey Smith, Ph.D. has discovered that orlistat, commonly prescribed as an anti-obesity drug, has a positive side-effect: it inhibits cancer growth. Dr. Smith made this discovery using an activity-based proteomics screening technique developed in his laboratory that makes it possible to identify active targets and simultaneously screen for their inhibitors. These results will be published in the journal Cancer Research on March 15.

The metabolism of a tumor cell is different from its normal counterpart cell. Scientists have long suspected that metabolism is connected to tumor progression. Dr. Smith and co-workers designed a proteomics screen based on monitoring the activity of a family of enzymes--serine hydrolyases--involved in metabolism. They used their screen to compare normal prostate cells with prostate cancer cells and discovered that the prostate cancer cells are affected by an increased activity of fatty acid synthase. Fatty acid synthase is the enzyme that converts dietary carbohydrate to fat.

The screen also identified orlistat, marketed by Roche as XenicalTM, as an inhibitor of fatty acid synthase.

These discoveries, made in vitro, held true when tested in mice. When they administered orlistat to mice bearing prostate tumors, the Smith laboratory discovered that the drug was able to inhibit tumor growth in mice. Further experiments confirmed that orlistat has no effect on normal prostate cells and no apparent side effects in the mice; it acts specifically as fatty acid synthase.

Additional screening of breast cancer and colon cancer cells revealed that fatty acid synthase activity is upregulated in these tumors, as well, presenting the possibility of designing new treatments for these cancers based on inhibiting the enzyme’s activity with orlistat or a new drug based on orlistat’s inhibitory activity.

Orlistat was originally developed as an inhibitor of pancreatic lipase. Pancreatic lipase is a member of the same enzyme family--the serine hyrdolases--used in Smith’s screening. It is involved in processing of fats in the digestive tract, which is how the drug prevents adsorption of dietary fat.

The method developed by Dr. Smith represents a quantum leap in drug discovery. So-called "activity-based" proteomics screening is a new frontier in medical research, based on applying information gleaned from the human genome project. The ability to compile a comprehensive profile of a potential drug’s activities, revealing unintended activities along with the intended behaviors targeted by the drug offers a systematic way to simulate how a drug will work, before it is actually tested in animals and humans.

Given the time and cost inherent in developing new treatments, activity-based proteomics screening opens up a new route for finding effective treatments based on monitoring basic cell behaviors, such as metabolism or respiration.

Proteomics screening is an efficient way to determine proof of concept needed before a potential treatment can be refined for clinical trials: in a matter of weeks, Dr. Smith was able to glean the initial discovery that linked excessive fatty acid synthase activity with flawed metabolism in cancer cells, and identified orlistat as its inhibitor.

"This discovery with orlistat has given us a very nice wedge with which we can go in and perturb tumor cells and ask the question, ’What are the active targets, what are the other changes that take place when you inhibit fatty acid synthase?’", says Dr. Smith, "and that will give us really good insights into the mechanism, and we anticipate that’s going to reveal a whole swath of additional drug targets along this pathway. This is a big advance in the sense that we have an approved drug--approved for one indication--that has another target and another potential disease indication, prostate cancer."

Dr. Smith is Associate Scientific Director for Technology at The Burnham Institute, where he is also a Associate Professor in the Institute’s NCI-designated Cancer Center.

Co-authors contributing to this study include Drs. Steven J. Kridel and Fumiko Axelrod, postdoctoral fellows at The Burnham Institute, and Dr. Natasha Rozenkrantz of Activix Biosciences in La Jolla.

This research was supported by grants from the National Cancer Institute, and the Department of Defense’s Prostate Cancer Program.

The Burnham Institute is an independent, nonprofit, public benefit organization dedicated to basic biomedical research principally in the areas of cancer, aging, and the neurosciences. The Institute ranks consistently among the world’s most influential research organizations for the impact of its research in analyses conducted annually by the Institute for Scientific Information.

Nancy Beddingfield | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

nachricht Breakthrough in Mapping Nicotine Addiction Could Help Researchers Improve Treatment
04.10.2016 | UT Southwestern Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Innovative technique for shaping light could solve bandwidth crunch

20.10.2016 | Physics and Astronomy

Finding the lightest superdeformed triaxial atomic nucleus

20.10.2016 | Physics and Astronomy

NASA's MAVEN mission observes ups and downs of water escape from Mars

20.10.2016 | Physics and Astronomy

More VideoLinks >>>