How do cancer cells “commit suicide”? New results may improve treatment

It is clear to us that cells die; This is part of the cycle of life. And there is also no doubt that there are two types of cell death: “random” and “programmed”, which could be considered as a kind of cell suicide.

The question currently occupied by researchers is to determine the process by which cancer cells end their days in the second way. Because a deep knowledge of the biochemical sources that influence this final act can help us stimulate our defenses against tumors.

Criteria for issuing a “death certificate”

In 2018, the Nomenclature Committee for Cell Death (NCCD) proposed to unify the criteria for defining cell death and its various typologies. Based on your testimony, we can certify this end when it loses its shell integrity, fragments, or is engulfed by neighboring cells.

The NCCD has also identified different types of cell death, which can be classified as follows, as stated at the beginning of the article:

• Unscheduled or necrosis. It is characterized by an increase in cell volume, swelling of its organelles (nucleus, mitochondria and other internal structures), membrane rupture and loss of cell contents.

• Planned. Various molecular signals activate the self-destruction countdown, the process by which the body purges unwanted cells.

In turn, programmed cell death can occur in two ways:

• Apoptosis. It is characterized by a number of changes in the cell. This retracts the elongations of the cytoplasm or pseudopod, thus acquiring a rounded appearance and decreasing in size. Its nucleus ruptures, pores form in the membrane that covers it, and it is eventually taken up by other cells.

• Non-apoptotic programmed cell death. Among the various modalities it covers is pyroptosis, which mainly affects cancer cells. This is associated with inflammatory processes and pathological cell death or necrosis.

This is how cancer cells die

When this last process is set in motion, the cells swell, the substance in the nucleus ruptures, and pores appear in the plasma membrane, which eventually rupture. At this time, the contents of the cell, along with substances that promote inflammation, are released outside.

It is important to know that pyroptosis occurs in two stages, which we can call initiating and effector. In the first case, the cells of the immune system produce two types of substances: one with an inflammatory effect (interleukins), and the other with an enzymatic effect (caspases). In the second phase, both types of compounds are activated by intracellular complexes called inflammasomes or inflammatory bodies.

While interleukins develop their inflammatory action, caspase activation leads to the formation of pores or cavities in the cell membrane, which leads to its destruction.

Promising discoveries

Numerous studies have linked chemotherapy given to fight cancer with a switch from apoptosis to pyroptosis. But also, as we have already seen, pyroptosis activates the cells of the immune system, and all this happens due to specific proteins.

From this, it can be concluded that cell death due to pyroptosis associated with pharmacological treatment may also act as a stimulus to enhance our cancer defense response. The mediator proteins will act as a powerful signal to activate immune cells, which will help shrink or suppress the tumor by inducing pyroptosis.

So far, according to most studies, the main one is a protein called gasdermin-E; many authors, in fact, think that the point here is only in him. Contrary to this prevailing opinion, some recent work has increased the number of proteins involved in this process and left the door open for others to open.

The bottom line is that cancer cells do not die simply because they have been exposed to chemotherapy drugs. Its final act is produced by a programmed mechanism, possibly mediated by various proteins. And these proteins don’t just cause cell death: they can also activate immune system cells that help fight tumors.

Salvador Mut Ronda, PhD. Director of the MA in Bioethics at VIU, International University of Valencia

This article was originally published on The Conversation. Read the original.