Penn researchers explore the role of cell suicide in the development and treatment of cancer

June 14, 2001

Study provides more evidence for a central role of mitochondria in apoptosis

Philadelphia, PA - Within the workings of a human cell there is an innate mechanism for self-destruction - a carefully choreographed act called apoptosis, or programmed cell death. Without apoptosis, diseased cells, especially cancerous cells, are not eliminated from the body and can continue to threaten other cells. Not surprisingly, cancer researchers are trying to piece together the mechanics of apoptosis and how they can use it against cancer cells.

In the June 15 issue of Genes and Development, researchers from the University of Pennsylvania School of Medicine identify the essential role of two pro-apoptotic proteins, Bax and Bak, in initiating apoptosis.

This new work demonstrates that cells lacking Bax and Bak cannot be killed by either chemotherapy or irradiation. It also demonstrates conclusively what scientists have suspected for several years: that chemotherapy and irradiation work to treat cancer by tricking the cancer cell into committing suicide.

This study is the third of a series of articles that researchers have published in recent months exploring the functional role of the Bcl-2 family of proteins - of which Bax and Bak are members - in regulating cell death.

"Within the Bcl-2 family of proteins, some proteins are actively pro-apoptotic while others are anti-apoptotic," said Craig B. Thompson, M.D., scientific director of the Abramson Family Cancer Research Institute at the Penn Cancer Center. "The result is a careful balance where one set of the proteins prevents the other from working."

In this new report Thompson and his colleagues demonstrate that this balancing act takes place on the surface of a cell's mitochondrion, which is the cellular organ devoted to converting sugars and fats into usable energy for the cell. In cells that lack Bak and Bax, the researchers demonstrate that virtually all forms of cell death are eliminated. Without Bax or Bak to turn off the function of the mitochondria, cells become immortal.

"Although we have known that damaged mitochondria can initiate apoptosis, the importance of mitochondria in this process has become a central issue," said Thompson. "We believe the new evidence demonstrates that the mitochondria plays a major role in all forms of apoptosis. This has important implications for the development of new cancer treatments as well as provides new hope that cell death can be prevented during a stroke or heart attack."

It is Bax and Bak, however, that are essential in carrying out the disruption of mitochondria. Interestingly, Bax and Bak are also redundant, as either protein - by itself - is effective in triggering apoptosis. According to Thompson, the redundant role of Bax and Bak represents a previously unknown but essential step in regulating apoptosis. "The fact that we have two separate proteins that do the same essential job stresses the importance of this step in controlling cell survival," said Thompson.

Bax and Bak also illustrate the overall complexity of the mechanism behind apoptosis. But by examining how individual parts of the mechanism function, the researchers hope to map out new ways to correct for the mechanism when it fails. "To look at it broadly, there are only two major types of diseases: ones where cells are killed and ones where cells refuse to die," said Thompson. "Cancer is one of the latter - it occurs when diseased cells that do not respond to apoptotic signals grow out of control. The trick is to find a way to get cancer cells to respond to those signals."
-end-
Contributors to this research include Wei-Xing Zong, PhD, and Tullia Lindsten, PhD, of the Abramson Family Cancer Research Institute at Penn and Andrea J. Ross, PhD and Grant R. MacGregor, PhD, of the Center for Molecular Medicine at the Emory University of School of Medicine.

Their research has been funded by the National Institutes of Health and The Leonard and Madlyn Abramson Family Cancer Research Institute at the University of Pennsylvania Cancer Center.

University of Pennsylvania School of Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.