New Platinum Compound Potentially More Effective At Destroying Cancer Tumors

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Main Category: Cancer / Oncology
Also Included In: Biology / Biochemistry
Article Date: 09 Dec 2009 - 2:00 PDT

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Researchers in the US have developed and tested a new platinum compound that appears to be more effective at destroying cancer tumors than cisplatin, a commonly used FDA-approved drug that is administered by itself or with other drugs to treat mostly advanced bladder, ovarian, testicular and other cancers.

The study is to be published in this week's issue of the Proceedings of the National Academy of Sciences, and is the work of chemists from the Massachusetts Institute of Technology (MIT).

Cisplatin is a platinum-based compound that causes DNA in cancer cells to crosslink and trigger cell death.

The new compound, called mitaplatin, is made from cisplatin and dichloroacetate (DCA), a substance that has the ability to select specific mitochondria in cancer cells and alter the way they function. By adding DCA, the chemists have in effect enhanced the cancer cell-killing abilities of cisplatin.

Mitochondria perform a number of vital cell functions, such as providing cells with chemical energy by making Adenosine-5'-triphosphate (ATP) and they also play an important role in regulating the cell life cycle, including death.

One of the ingredients the mitochondria use to make ATP is glucose, and in cancer cells, the mitochondria are altered in such a way that they metabolize glucose differently to normal cells.

DCA targets only those cells whose altered mitochondria produce glucose differently and then causes them to commit suicide by changing the signals produced by the mitochondria, leaving normal cells intact.

The MIT chemists designed mitaplatin so that once it is inside a cell it releases cisplatin and two units of DCA by intracellular reduction. Thus by the addition of DCA, mitaplatin delivers a double blow to the cancer cell: cisplatin attacks the DNA and DCA attacks the mitochondria, with each attack designed to trigger cell death.

Co-author Stephen Lippard, the Arthur Amos Noyes Professor of Chemistry at MIT, told the media that:

"This differential effect conveys on mitaplatin the ability to kill cancer cells selectively in a co-culture with normal fibroblast cells, the latter being unaffected at the doses that we apply."

So far the MIT researchers have been working with cell cultures, although they have also shown that rats can tolerate mitaplatin at higher doses than cisplatin, and they have started examining the effects on mice transplanted with human tissues.

If those results show promise, they hope to show how the compound performs as a cancer therapy.

. "Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate."
Shanta Dhar and Stephen Lippard.
PNAS, (anticipated publication week beginning 7 Dec 2009).

Sources: MIT, National Cancer Institute.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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