Featured Research

from universities, journals, and other organizations

Researchers Identify A New Class Of Anti-cancer Drugs Based On Platinum

Date:
January 5, 2006
Source:
Virginia Commonwealth University
Summary:
Researchers at Virginia Commonwealth University's Massey Cancer Center have created a new platinum-based, anti-cancer agent able to overcome acquired drug resistance by first modifying the way it is absorbed into cancer cells and then attacking the DNA of those cancer cells.

Researchers at Virginia Commonwealth University’s Massey Cancer Center have created a new platinum-based, anti-cancer agent able to overcome acquired drug resistance by first modifying the way it is absorbed into cancer cells and then attacking the DNA of those cancer cells.

The findings may help researchers design a new generation of anti-cancer drugs that selectively target cancer cells, reduce resistance and side effects and expand the range of tumors that can be treated by platinum.

In the Dec. 26 issue of the journal Inorganic Chemistry researchers reported on the design of a new trinuclear platinum compound and demonstrated that its cellular absorption is significantly greater than that of neutral cisplatin, as well as other multi-nuclear platinum compounds. The enhanced uptake into cancer cells takes advantage of weak molecular interactions on the cells’ surface. These results underscore the importance of the new compound’s “non-covalent” interactions, prior to the attack on DNA. Non-covalent interactions minimize potential side reactions and produce changes in the structure of proteins and DNA, which is different from currently used drugs. This research was selected as the cover article for the print version of the journal, Issue 26.

Researchers compared the cytotoxicity and cellular concentrations of three anti-cancer drugs including the phase II clinical drug, BBR 3464, cisplatin and the new trinuclear platinum compound. In a laboratory model, human ovarian cancer cells were exposed to each drug.

“In platinum antitumor chemistry our objective is to design and develop complexes acting by new mechanisms of action,” said Nicholas Farrell, Ph.D., professor and chair in the Department of Chemistry at VCU, and lead author of the study. “Resistance to current drugs is due to poor cellular absorption and an increased ability of the cell to process or repair the damage caused by the chemotherapeutic agent.”

“Our novel compound was designed to overcome resistance by emphasizing new modes of DNA binding, and in the process we have found that the amount of platinum drug entering cells is increased,” he said. “The effectiveness of a platinum drug in killing cells is directly related to its concentration inside the cell.”

DNA-damaging agents, such as cisplatin, are among the most effective classes of compounds in clinical use for the treatment of cancer. The principal function of cisplatin is to bind to DNA. Platinum drugs are the largest class of anti-cancer drugs in the clinic and the most important in terms of treatment. Cisplatin is a chemotherapy drug that is given for the treatment of metastatic testicular or ovarian cancers, and some advanced bladder cancer, and is a very effective drug in combination with other therapies.

However, according to Farrell, these current agents have limited activity against many common human cancers, and they are susceptible to acquired drug resistance. He added that resistance to cisplatin has become a clinically relevant issue – especially for patients battling ovarian cancer because they develop resistance to cisplatin at a rapid rate.

Farrell said that use of the “non-covalent” approach and emphasizing cell uptake may help minimize the side effects of current platinum drugs. He said that both cell uptake and the ability of the cell to minimize the effect of DNA attack, or DNA repair, play a critical role in cellular resistance to cisplatin by altering its ability to effectively kill tumor cells. By understanding the features of cisplatin that contribute to resistance, Farrell and his team designed the new compound to circumvent these problems.

This work was supported by a grant from the National Institutes of Health. The study can be accessed via http://pubs3.acs.org/acs/journals/toc.page?incoden=inocaj&indecade=0&involume=44&inissue=.

Researchers in the VCU departments of chemistry and biology, and the Department of Pharmacology and Toxicology in the VCU School of Medicine collaborated on this research. Researchers included Amanda L. Harris, Ph.D.; Xiaohong Yang, Ph.D.; Alex Hegmans, Ph.D.; Lawrence Povirk; and John J. Ryan, Ph.D. Lloyd Kelland, Ph.D., from the Institute of Cancer Research in England also contributed to this work.


Story Source:

The above story is based on materials provided by Virginia Commonwealth University. Note: Materials may be edited for content and length.


Cite This Page:

Virginia Commonwealth University. "Researchers Identify A New Class Of Anti-cancer Drugs Based On Platinum." ScienceDaily. ScienceDaily, 5 January 2006. <www.sciencedaily.com/releases/2006/01/060104232218.htm>.
Virginia Commonwealth University. (2006, January 5). Researchers Identify A New Class Of Anti-cancer Drugs Based On Platinum. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2006/01/060104232218.htm
Virginia Commonwealth University. "Researchers Identify A New Class Of Anti-cancer Drugs Based On Platinum." ScienceDaily. www.sciencedaily.com/releases/2006/01/060104232218.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins