Innovative compound uses new mechanism to kill cancer cells

A team from Bochum has developed a compound that triggers the death of cancer cells through ferroptosis. It is promising for new cancer therapies, but still needs to be further developed to attack only cancer cells.

A team from Bochum has developed a substance for the first time that can trigger ferroptosis, a specific form of cell death, in cancer cells. This breakthrough could lead to the development of new drugs.

The research was carried out in the Medical Inorganic Chemistry group of Dr. Johannes Karges in collaboration with PhD student Nicolás Montesdeoca and two bachelor students, Lukas Johannknecht and Elizaveta Efanova, and with the support of Dr. Jaqueline Heinen-Weiler from the Center for Medical Imaging at the Ruhr University Bochum.

Two types of programmed cell death

In programmed cell death, certain signaling molecules start a kind of suicide program to cause cells to die in a controlled manner. This is a necessary step, for example, to eliminate damaged cells or to control the number of cells in certain tissues.

Apoptosis has long been known as a mechanism of programmed cell death. Another mechanism that has only recently been discovered is ferroptosis, which, unlike other cell death mechanisms, is characterized by the accumulation of lipid peroxides. This process is typically catalyzed by iron – Latin ferrum – hence the name ferroptosis.

“In our search for an alternative to the mechanism of action of conventional chemotherapeutic agents, we specifically looked for a substance that can trigger ferroptosis,” explains Johannes Karges. His group synthesized a cobalt-containing metal complex that accumulates in the mitochondria of cells and produces reactive oxygen there. speciesmore precisely, hydroxide radicals. These radicals attack polyunsaturated fatty acids, producing large amounts of lipid peroxides, which in turn trigger ferroptosis. The team was the first to produce a cobalt complex that is designed to specifically trigger ferroptosis.

Efficacy demonstrated on artificial microtumors

The Bochum researchers used various cancer cell lines to show that the cobalt complex triggers ferroptosis in tumor cells. In addition, the substance slowed the growth of artificially created microtumors.

“We are convinced that the development of metal complexes that trigger ferroptosis is a promising new approach for cancer therapy,” says Johannes Karges, summarizing the research, adding: “However, there is still a long way to go before our investigations result in a drug.” The metal complex must first prove its effectiveness in animal experiments and clinical tests. In addition, the substance does not currently specifically attack tumor cells, but would also attack healthy cells. The researchers must therefore first find a way to package the cobalt complex in such a way that it only damages tumor cells.

Reference: “Ferroptosis Inducing Co(III) Polypyridine Sulfasalazine Complex for Therapeutically Enhanced Anticancer Therapy” by Nicolás Montesdeoca, Lukas Johannknecht, Elizaveta Efanova, Jacqueline Heinen-Weiler and Johannes Karges, August 13, 2024, Angewandte Chemie International Edition.
DOI: 10.1002/anie.202412585

Johannes Karges is supported by a Liebig Fellowship from the Chemical Industry Fund as well as the Life Sciences Bridge Award from the Aventis Foundation and the Paul Ehrlich & Ludwig Darmstaedter Early Career Award 2024.