March 13, 2012

Researchers Aim To Reduce Harmful Effects Of Chemotherapy

Researchers at Duke University have determined the structure of a key molecule used to carry chemotherapy and other anti-viral drugs into cells. This discovery could help create drugs that work more effectively, without harming healthy cells or tissue.

The researchers published the article with their findings on March 11, 2012 online in Nature.

The senior author of these findings and assistant professor of biochemistry, Seok-Yong Lee, PhD said in the article “Knowing the structure and properties of the transporter molecule may be the key to changing the way that some chemotherapies, for example, could work in the body to prevent tumor growth.”

The molecule in question, called a concentrative nucleoside transporter, works by moving nucleosides from outside cells to the inside of cells. Nucleosides are the foundations of both DNA and RNA. When these nucleoside-like drugs are entered into the cells, they turn into nucleotides. It is then that these drugs are incorporated into the DNA, preventing tumor cells from dividing.

Knowing the shape and structure of these transporter molecules will help to create even better nucleoside drugs. “We discovered the structure of the transporter molecule, and now we believe it is possible to improve nucleoside drugs to be better recognized by a particular form of the transporter molecule that resides in certain types of tissue,” Lee said. “Now we know the transporter molecule has three forms, which recognize different drugs and reside in different tissues.”

By determining the shape of the transporter molecule, scientists can improve the types of drugs used in chemotherapy as well as use the drugs more efficiently.

Lee, who is also a member of the Duke Ion Channel Research Unit, said ““¦ if you can improve the interactions between the transporter and the drug, you won´t need as much of the drug to get it into the tumor cells efficiently,” Lee said. “Knowing the shape of the transporters will let scientists design drugs that are recognized well by this transporter.”

Since the drugs enter the cells as tumor cells, a lower dose would not only be effective on tumor cells, but would also be safer for the existing healthy cells. According to Lee, “Healthy cells don´t divide as often as tumor cells, so lowering the amount of drug given overall would be an effective approach to killing tumors while protecting patients.”

While researching transporter molecules, the Duke researchers studied transporter molecules from a comma-shaped bacterium called Vibrio cholera. As these bacterium share similar amino acid sequences, these bacterial transporters provided a good model for studying human transporters. Both human transporters and the bacterial transporters use a sodium gradient to import the nucleosides and drugs into the cells.

With this research completed, the team now hopes to understand which features of the transporter cells have the ability to recognize chemo drugs. Ultimately, the team hopes to design drugs that can easily enter cells.

Dr. Lee won an award for his work and contribution to this project. He received the National Institute of General Medical Sciences Award at the Biophysical Society last month.


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