New ruthenium complexes target cancer cells without typical side effects

May 28, 2013
A graphic from the Molecular Cancer Therapeutics paper shows the growth of a control tumor compared to the growth of tumors treated with ruthenium-based complexes developed in the lab. Credit: UT Arlington

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 chemotherapies.

Fred MacDonnell, professor of chemistry and biochemistry at The University of Texas at Arlington, has been researching a new generation of metal-based antitumor agents along with a team from the City of Hope Comprehensive Center Center in Duarte, Calif. Their aim is to find new therapies to complement widely used platinum-based therapies, such as cisplatin. Cisplatin is one of the most widely used anti-cancer drugs and shows remarkable effectiveness against some cancers, however it does not work on all cancers and can have severe side effects.

In a study published in the May edition of Molecular Cancer Therapeutics, the team describes two newly developed ruthenium polypyridyl complexes, or RPCs, that yielded results comparable to cisplatin against human non-small cell in pre-clinical lab tests.

Unlike cisplatin, the RPCs were generally cleared from the body unchanged, without noticeable effects on metabolism or . In lab tests, healthy cells could withstand almost 10 times as much exposure to the team's ruthenium complexes as the cancer cells.

The study also found that the RPCs seemed to target cells in hypoxic states. Hypoxia, or low oxygen, is a signature of tumor cells.

" on the market now generally are less effective under hypoxic conditions or insensitive to the ," MacDonnell said. "Since many are under hypoxic stress and most normal cells are not, having something that becomes even more effective under hypoxia could have some real benefit to the patient."

The effectiveness of the RPCs tested seems to be associated with a particular portion of their structure. This portion, known as "tatpp" is redox-active, which means it is reduced when bound to DNA in the normal cellular environment. MacDonnell's team believe that this reduction step in the DNA bound compound sets in motion a biological process that triggers apoptosis, also known as programmed cell death, in cancer cells. Under , this reduction is more prevalent, leading to greater cell death in those cells.

"Being activated under low-oxygen conditions makes these unique complexes excellent candidates for use on some of the most difficult to treat tumors," said Dr. Sanjay Awasthi, professor of medical oncology and therapeutics research at City of Hope. "Now that we have demonstrated the role of the tatpp ligand in these biological processes, our team can continue toward the goal of using ruthenium-based complexes to enhance current treatments."

MacDonnell said the ruthenium complexes' increased effectiveness against malignant cells could be because the complexes can more easily enter cancer cells, which tend to be more metabolically active than normal cells. That hypothesis, however, is something the team will explore with further research.

Explore further: New ruthenium-based drugs show promise for killing cancer cells

More information: The paper, called "Regression of lung cancer by hypoxia-sensitizing ruthenium polypridyl complexes," is available online at: mct.aacrjournals.org/content/12/5/643.short

Related Stories

New ruthenium-based drugs show promise for killing cancer cells

June 11, 2012
A new study by University of Kentucky researchers shows how light and strained ruthenium-based drugs may be more effective at fighting cancer cells and less toxic to healthy cells than a similar and widely used drug.

Resistance is futile: Researchers identify gene that mediates cisplatin resistance in ovarian cancer

April 15, 2013
Platinum compounds, such as cisplatin and carboplatin, induce DNA cross-linking, prohibiting DNA synthesis and repair in rapidly dividing cells. They are first line therapeutics in the treatment of many solid tumors, but ...

Cisplatin-resistant cancer cells sensitive to experimental anticancer drugs, PARP inhibitors

April 3, 2013
Poly (ADP-ribose) polymerase inhibitors may be a novel treatment strategy for patients with cancer that has become resistant to the commonly used chemotherapy drug cisplatin, according to data from a preclinical study published ...

Study reveals how melanoma evades chemotherapy

April 8, 2013
Nitric oxide (NO), a gas with many biological functions in healthy cells, can also help some cancer cells survive chemotherapy. A new study from MIT reveals one way in which this resistance may arise, and raises the possibility ...

Lack of oxygen in cancer cells leads to growth and metastasis

September 13, 2012
(Medical Xpress)—It seems as if a tumor deprived of oxygen would shrink. However, numerous studies have shown that tumor hypoxia, in which portions of the tumor have significantly low oxygen concentrations, is in fact linked ...

Scientists define a new mechanism leading to tumor hypoxia

May 9, 2013
An article published recently in Tumor Microenvironment and Therapy - an open access journal by Versita, defines a novel mechanism of tumor hypoxia induced by the longitudinal gradient of residual oxygen along tumor vessels ...

Recommended for you

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

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 ...

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.