Smac Causes Cancer Cells to Commit Suicide, Research Says

Researchers affiliated with the Howard Hughes Medical Institute have developed a compound that triggers a suicide message to cancer cells, hopefully leading the way to more targeted treatments that will cause cancer cells to self-destruct, and leaving healthy cells alone.

The molecule developed by a team led Xiaodong Wang is at the University of Texas Southwestern Medical Center mimics a naturally occurring protein called Smac, which causes some types of cancer cells to switch from reproduction mode into dying.

The body naturally triggers individual cell death when faulty reproduction happens, or if the cell is redundant. The process of suicidal cell death is called apoptosis, and the suicide signal is sent to the cell by its own mitochondria via the Smac protein. The self-induced cell death part of the body's natural balancing act.

Wang and his team developed a series of artificial molecules that shared a similar molecular signature as Smac, and introduced them to cultures of cancer tissues. They discovered that when the artificial compound was introduced to cancer cells with TNFα present, the mimetic compound caused the shrinkage of the cell lines, and sometimes their complete disappearance.

TNFα stands for tumor necrosis factor, and plays a key role in the body's natural immune response, and are produced primarily by macrophages which constantly roam the body and literally consume foreign organisms and materials. TNFs when triggered also cause inflammation in the area where they are released, and cause the body to rally additional resources to the affected location.

The researchers were puzzled by the involvement of TNF with the suicide signal, since the presence of TNF alone usually gives cancer cells a pro-survival edge. Wang's team found that some cancer lines were killed by the artifical Smac only when TNFα was present, while certain types of breast cancer and melanoma were killed the Smac-like molecule working alone.

"Thus, in these cancer cell lines, the TNFα survival advantage turns out to be a fatal flaw, because the same pathway can be switched to apoptosis by Smac mimetics," Wang said in a press release form Howard Hughes Medical Institute. "So, for some cancers, we might be able to use Smac mimetics as a single treatment agent. And we can use the presence of TNFα as a marker to tell us which tumors will respond to the Smac mimetic alone."

Wang's team is hopeful they will develop new cancer therapies as a consequence of their research. Their findings are in the November 2007 issue of the journal Cancer Cell.