Platinum Compounds Fight Against Cancer

Connie K. Ho for – Your Universe Online

Researchers at the Massachusetts Institute of Technology (MIT) recently revealed a new platinum compound that could eliminate cancer cells more effectively than cisplatin, a popular chemotherapy anticancer drug. Drugs that have platinum are the most widely used most powerful cancer drugs. On the downside, these agents have toxic side effects and the cancer cells can eventually become resistant; as such, the new discovery is exciting for researchers to explore new treatment possibilities.

Researchers hope that the new compound will prove to be affective in fighting cancer.

“I´ve long believed that there´s something special about platinum and its ability to treat cancer,” noted MIT chemistry professor Stephen J. Lippard, who has studied platinum drugs, in a prepared statement. “We might have a chance of applying platinum to a broader range of cancer types, more successfully.”

The project is described in a paper featured in the Proceedings of the National Academy of Sciences (PNAS). Lippard, senior author of the paper, has examined the workings of cisplatin and similar drugs for many years in hopes that these drugs would be more powerful, not as many side effects, and overcome cancer-cell resistance. Lippard and the team of researchers looked at compounds that were similar to cisplatin. Cisplatin can treat testicular cancer, ovarian cancer, lymphoma, as well as some lung tumors. The compound becomes positive charged when it enterers a cancerous cell as it replaces its chloride ions. The positive ion can then take on the negative charged DNA, producing cross-links with DNA strands and creating difficulties for the cell to gather information about that part of the DNA. This change causes much damage to the cell and the cell can be eliminated if not repaired.

In the past, scientists also thought that platinum compounds required two DNA binding sites to be able to influence cancer cells. However, researchers discovered in the 1980s that some positively charged platinum compounds could only bind to DNA at one site to activate anti-cancer activity. As such, instead of using cisplatin, the researchers looked at compounds that only had one replace chlorine atom, which would allow the compound to bind to DNA at one site instead of two. In 2008, Lippard and other scientists looked at pyriplatin, a compound that had one of the chlorine atoms of cisplatin replaced by a six-membered pyridine ring that had one nitrogen atom and five carbon atoms. Even though the compound wasn´t as strong as cisplatin, it showed some anti-cancer activity.

With these findings, Lippard focused on creating similar compounds that had larger rings. He believed that these rings would allow the compounds to be stronger in stopping DNA transcription from occuring. The compound ended up being phenanthriplatin, which was compared against 50 other types of cancer cells under the National Cancer Institute´s cancer-drug screening program. Phenanthriplatin was discovered to be four to 40 times stronger than cisplatin, deepening on the cancer cell. It also proved to have a different pattern of activity than cisplatin, which demonstrated that it could possibly be used to treat cancers that were resistant against cisplatin.

Furthermore, the researchers believe that phenanthriplatin has many advantages. For one, it can target cancer cells with fewer difficulties than cisplatin. It also can have the ability to inhibit transcription, making it difficult for the cells to change RNA to DNA in gene expression. Lastly, the compound can shield against cancer cells´ defenses. Phenanthriplatin has bulky three-ring attachments that can stop sulfur from stopping it from working effectively.

Researchers unaffiliated with the study believe that the new compound is a positive step forward.

“It expands the utility of platinum drugs and avoids some of the problems that existing drugs have,” remarked Luigi Marzilli, a professor of chemistry at Louisiana State University, in the statement.

In continuing the research, the investigators are conducting animal tests to understand how effective the drug is in killing tumors and how it moves through the body.