Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How Does the Antitumor Drug Get to the Cell Nucleus?

30.10.2007
Copper transporter plays an unexpected role in the absorption of cisplatin

Platinum complexes such as the well-known cisplatin are powerful antitumor medications.

They cross the cell membrane and reach the nucleus, where they attach to DNA and stop cell growth. But how does cisplatin get to the nucleus? Italian researchers have now proven that a copper transport protein may play a critical role. In the journal Angewandte Chemie, they present their hypothesis about the transport mechanism.

It has always been assumed that cisplatin simply passes through the cell membrane; however, growing evidence indicates that a copper transporter is involved. Ctr1 is a membrane-dwelling protein that brings copper into cells. It consists of three helical segments that sit in the membrane, one end protruding into the cell, the other on the outside. Three such molecules lodge together to form a channel-like structure. The end that sticks out of the cell and the interior of the “channel” contain many sulfur-containing methionine groups, which are important for binding copper.

... more about:
»Cisplatin »Platinum »Protein »Transporter »copper

A team led by Giovanni Natile at the University of Bari (Italy) has now proven that this structural element also plays a role in binding platinum. The researchers produced a synthetic peptide with a structure very similar to the extracellular end of the copper transport protein. Cisplatin is a complex with a central platinum ion and four ligands: two neighboring amino groups and two neighboring chloride ions. The peptide displaces all four of these ligands and binds to the platinum ion itself.

As is the case for copper, the transport protein seems to bind the platinum atom from cisplatin by replacing all other ligands bound to the metal ion. The next step could be the traversal of a ligand-free “naked” platinum atom through the channel and into the cytosol of the cell. However, this contradicts other experiments that have demonstrated that treated tumor cells do not contain bare platinum, but rather undegraded cisplatin—accumulated in certain organelles.

Natile and his co-workers have proposed an interesting hypothesis to explain these observations: After an initial interaction between a few cisplatin molecules and the methionine-rich extracellular end of the copper transporter, the platinum ion does not pass through the channel, but instead stabilizes the trimeric channel structure. This sets in motion a mechanism called endocytosis, in which the cell membrane encircles the transporter and forms a little interior bubble filled with the outer medium. This medium contains some intact cisplatin. The bubble then migrates to the interior of the cell and comes into contact with the organelles, including the nucleus.

Author: Giovanni Natile, Università degli Studi di Bari (Italy), mailto:natile@farmchim.uniba.it

Title: Interaction between Platinum Complexes and a Methionine Motif Found in Copper Transport Proteins

Angewandte Chemie International Edition, doi: 10.1002/anie.200703271

| Angewandte Chemie
Further information:
http://pressroom.angewandte.org

Further reports about: Cisplatin Platinum Protein Transporter copper

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>