Cancer cells die "iron death"
Many tumors are susceptible to ferroptosis – a variant of cell death in which iron is involved. Does this offer a new approach to cancer therapies?
Just like humans, individual cells in the body can die in different ways. The sudden accidental death of a person could be compared, at the cellular level, to necrosis, in which cells, due to severe damage (to their plasma membrane, for example), literally rupture and release their contents into the environment. In contrast, apoptosis – “programmed cell death” – is more like a meticulously planned suicide: the cell components are broken down in a specified order, packed into small membrane-enclosed vesicles and disposed of by the immune system.
Between the extremes of chaotic necrosis and carefully coordinated apoptosis lie a number of other variants of demise, as researchers have discovered over the past few years. They are types of death with ancient Greek names such as necroptosis, netosis or entose. The newest member of this list is called Ferroptosis.
When the chemist Brent Stockwell was looking for substances that specifically attack tumor cells in his laboratory at the Whitehead Institute for Biomedical Research in Cambridge (Massachusetts) in 2003, he initially had no idea that he was encountering a completely new type of cell death would. He had focused on small molecules that detect a malformation of the RAS protein - a protein that is frequently altered in cancer. Stockwell found a substance he called erastin that caused cancer cells to break down quickly. However, this happened in a peculiar way: unlike in necrosis or apoptosis, some cell components shrank while the membranes seemed to condense and disintegrate. Above all, however, the process depended on the presence of iron ions and was accompanied by a large increase in reactive lipid peroxides. If Stockwell intercepted the free iron with special molecules, this prevented the accumulation of lipid peroxides and cell death at the same time. A team led by Marcus Conrad from the Helmholtz Zentrum München made similar observations, working with modified mouse brain cells …
