Study suggests new approach to fight lung cancer

June 18, 2013

Recent research has shown that cancer cells have a much different – and more complex – metabolism than normal cells. Now, scientists at The University of Texas at Dallas have found that exploiting these differences might provide a new strategy to combat lung cancer.

In an article published online May 21 in the journal PLOS ONE, UT Dallas researchers compared the metabolic characteristics of non-small-cell lung cancer cells with normal taken from the same patient.

They found that the cancer cells consumed substantially more oxygen than normal cells, about two and a half times as much. The lung cancer cells also outpaced their normal counterparts in synthesizing a critical chemical called heme.

Heme is an iron-containing molecule that is a component of a variety of hemoproteins, which transport, store and use oxygen throughout the body, among other functions. These proteins directly regulate many processes involved in , converting oxygen to the energy that cells need to thrive. For example, heme binds to and transports oxygen to cells via the familiar .

"We reasoned that the enhanced we found in lung cancer cells might be attributable to increased levels of heme and hemoproteins," said Dr. Li Zhang, professor of at UT Dallas and senior author of the paper.

To test this possibility, Zhang and biology graduate student Jagmohan Hooda measured and compared the levels of heme that lung cancer cells synthesize and the amount that normal lung cells make.

"All cells need a certain level of heme, but our findings indicate that normal cells need much less heme compared to cancer cells," Zhang said. "We think a high level of heme in cancer cells results in a lot more hemoproteins, which metabolize oxygen and produce more . That then drives the cancer cells to proliferate, to migrate and to form colonies.

"Cancer cells not only make significantly more heme, we also found they uptake more heme from the blood," said Zhang, who holds the Cecil H. and Ida Green Distinguished Chair in Systems Biology Science.

Zhang and Hooda then treated the matched set of lung cancer and normal lung cells with a heme inhibitor called succinyl acetone. The chemical blocks cells from synthesizing heme.

Other researchers have previously studied the ability of succinyl acetone to inhibit growth of various types of cancer cells, but until the UT Dallas study, Zhang said it was not known whether those effects were unique to cancer in general or how the compound might affect normal cells.

"Before our study, scientists didn't know whether there was any difference in effect between cancer cells and normal cells," Zhang said. "Now we know that this compound doesn't have much effect on normal cells, but it does have an effect on lung cancer cells."

Inhibiting the cancer cells' ability to produce heme affected those cells dramatically, said Hooda, who was the lead author of the study.

"Suppressing heme availability reduced the lung cancer cells' ability to use oxygen, and hence the cells' ability to proliferate and migrate," he said. "The cultured cancer cells we studied stopped proliferating and eventually died."

Zhang said a key finding was that normal cells don't need that much heme to function properly.

"When you inhibit heme synthesis or deplete heme, it doesn't affect normal cells too much," she said. "It selectively affects cancer cells. That's the beauty of our work.

"Because inhibiting heme effectively arrested the progression of , our findings could positively impact research on lung cancer biology and therapeutics."

The National Cancer Institute estimates that 228,000 new cases of will be diagnosed and more than 159,000 deaths from the disease will occur in the U.S. in 2013.

Although more research is needed before new therapies might be developed from the findings, Hooda said the heme-inhibiting technique would likely not be toxic to humans, noting that succinyl acetone would not need to eliminate all heme synthesis in the body.

"Even after lowering heme levels to the point that are affected, it's likely that would live on with a small amount of heme," Hooda said.

Explore further: 'Chase and run' cell movement mechanism explains process of metastasis

Related Stories

'Chase and run' cell movement mechanism explains process of metastasis

June 16, 2013
A mechanism that cells use to group together and move around the body – called 'chase and run' - has been described for the first time by scientists at UCL.

Diabetes drug makes lung cancer vulnerable to radiotherapy

May 1, 2013
The diabetes drug metformin slows the growth of lung cancer cells and makes them more likely to be killed by radiotherapy, according to a study published in the British Journal of Cancer today.

New ruthenium complexes target cancer cells without typical side effects

May 28, 2013
A team of UT Arlington researchers has identified two ruthenium-based complexes they believe could pave the way for treatments that control cancer cell growth more effectively and are less toxic for patients than current ...

Rice-cell cocktail kills cancer cells, leaves normal cells alone

January 14, 2013
(Medical Xpress)—Juice from rice cells knocked out two kinds of human cancer cells as well or better than the potent anti-cancer drug Taxol in lab tests conducted by a Michigan Technological University scientist. Plus, ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.