Navigation Links
Smac-ing lung cancer to death

Howard Hughes Medical Institute researchers have developed a small molecule that can turn the survival signal for a variety of cancer cells into a death signal. The molecule mimics the activity of Smac, a protein that triggers the suicide of some types of cancer cells.

The researchers say their findings suggest that Smac-mimetic compounds could be useful as targeted cancer treatments for lung and other cancers. Such therapy may be less toxic to healthy cells than current compounds used in cancer chemotherapy.

The researchers, led by Howard Hughes Medical Institute investigator Xiaodong Wang, published their findings in the November, 2007, issue of the journal Cancer Cell. Wang is at the University of Texas Southwestern Medical Center.

Cells that are defective or that become unnecessary during growth and development are induced to commit suicide through a finely balanced process known as apoptosis, or programmed cell death. A protein called Smac, which is a shortened version of second mitochondria-derived activator of apoptosis, is a part of the cells programmed cell death machinery. When that machinery is switched on, Smac is released from the mitochondria and triggers the pathway that kills damaged or abnormal cells. Cancer cells, however, can survive Smacs death signal by switching off the apoptotic machinery.

To see if they could get around this problem, Wang and other researchers have developed small-molecule mimetics of Smac that can enter the cell and trigger apoptosis. These mimetic molecules do their damage without the need for the Smac signal from the mitochondria. In earlier studies, Wang and his colleagues found that a Smac mimetic that they developed in the lab could kill cancer cells in culture. But they found that the cancer cells are only killed when the mimetic molecule is introduced in conjunction with another component of the apoptotic machinery known as TNF.

In the new studies published in Cancer Cell, Wang and his colleagues found that a significant percentage of human non-small-cell lung cancer cell lines were sensitive to treatment by the Smac mimetic alone. When the researchers introduced those sensitive cells into mice and allowed them to produce tumors, they found that the Smac mimetic caused the tumors to regress and, in some cases, even disappear.

These findings made us wonder what it was about these cell lines that made them sensitive to the Smac mimetic alone, said Wang. Cancer cells are hard to kill, but these cell lines seemed to have already become sensitized to apoptosis.

The researchers studies revealed that the sensitive cell lines produced their own TNF, so they were already primed for apoptosis. The paradox, said Wang, is that TNF signaling is also part of a complex pathway that gives cancer cells a survival signal, offering them a growth advantage. The researchers also found that some breast cancer and melanoma cell lines were sensitive to the Smac mimetic alone.

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

People have been suspecting for a long time that some cancer cells may somehow turn on their apoptotic pathway already, said Wang. And now we know what pathway they turn on and why. We can take advantage of this phenomenon for potential cancer therapy by switching a signal into a deadly one with Smac mimetics.


Contact: Jennifer Michalowski
Howard Hughes Medical Institute

Related medicine news :

1. Conventional prognostic factors fail to explain better prostate cancer survival in most Asian men
2. Survival differences by race most apparent in advanced stages of breast cancer
3. MRI finds breast cancer before it becomes dangerous
4. Investigators uncover intriguing clues to why persistent acid reflux sometimes turns into cancer
5. Pathway links inflammation, angiogenesis and breast cancer
6. Radiologists encouraged to look beyond cancer for clinically unseen diseases
7. Diet high in meat, fat and refined grains linked to risk for colon cancer recurrence, death
8. Immune deficiency linked to a type of eye cancer
9. Drop in breast cancer incidence linked to hormone use, not mammograms
10. Breast cancer prevention practices vary across Canada
11. First biomarker discovered that predicts prostate cancer outcome
Post Your Comments:
(Date:11/30/2015)... NC (PRWEB) , ... November 30, 2015 , ... ... practices in 2016. In 2016, expected coding changes are likely to include new ... service codes. It’s not easy to understand the effects of code changes in ...
(Date:11/29/2015)... ... November 30, 2015 , ... ... new company, Sublime Beauty NATURALS®. All products are available on Amazon or its ... oils, organic facial serums and USDA Certified Organic Sesame Oil for Oil Pulling," ...
(Date:11/29/2015)... (PRWEB) , ... November 29, 2015 , ... NewsWatch featured ... technology products available to consumers. Amanda Forstrom, a technology expert and special reporter for ... be a reality in the future. , It’s the future because flying cars are ...
(Date:11/29/2015)... CA (PRWEB) , ... November 29, 2015 , ... ... all new and unique analog distortion effect tool designed specially for Final Cut ... footage, and create limiltess looks with the easy-to-use modification controls. Destoying and creating ...
(Date:11/28/2015)... ... 28, 2015 , ... Safe storage for contraceptive devices may not always be ... New Jersey and the other from Bradley Beach, New Jersey, there is an easy ... of having to replace NuvaRings more often than necessary. As such, it affords peace ...
Breaking Medicine News(10 mins):
(Date:11/29/2015)... Iowa , Nov. 29, 2015 ... ultrasound guidance technology at the Radiological Society of ... in Chicago November 29 ... system is designed to offer customers unrivaled versatility, ... --> ...
(Date:11/27/2015)... YORK , November 27, 2015 ... system is set to go online. The potential to ... processes is vast and far from fully exploited as ... to patient health records, either via mobile tablet or ... ) --> ) --> ...
(Date:11/27/2015)... Research and Markets ( ) has ... Market 2015-2019" report to their offering. ... report, the author the present scenario and growth prospects ... calculate the market size, the report considers revenue generated ... IUDs and copper IUDs. The report forecasts the global ...
Breaking Medicine Technology: