Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Compound from Chinese medicine shows promise in head and neck cancer

20.04.2005


A compound derived from cottonseed oil could help improve the effectiveness of chemotherapy at treating head and neck cancer, researchers at the University of Michigan Comprehensive Cancer Center have found.



The findings, which will be presented Tuesday, April 19, at the American Association for Cancer Research annual meeting, could lead to a treatment that provides an effective option to surgically removing the cancer, helping patients preserve vital organs involved in speech and swallowing.

While new treatments in head and neck cancer have allowed some patients to undergo chemotherapy and radiation therapy instead of surgery, this form of cancer is often resistant to chemotherapy. When the cancer does not respond to these powerful drugs, patients must resort to surgery.


"Patients really benefit long-term by avoiding surgery because the side effects of surgery for head and neck cancer can be particularly difficult for patients – it’s how you talk, and how you swallow and how you breathe," says Carol Bradford, M.D., professor of otolaryngology at the U-M Medical School and co-director of the Head and Neck Oncology Program at the U-M Comprehensive Cancer Center.

The compound, (-)-gossypol, works to regulate a protein called Bcl-xL that’s overexpressed in cancer cells and makes these cells survive when they shouldn’t. Shaomeng Wang, Ph.D., co-director of the Molecular Therapeutics Program at the U-M Comprehensive Cancer Center, discovered (-)-gossypol, a compound derived from a component of Chinese medicine. Gossypol comes from cottonseed oil and was once used in China as a male contraceptive. More recently, it’s been tested as a cancer treatment. Wang found the negative isomer of gossypol binds at a site to block the active Bcl-xL protein. A prior study conducted by researchers in the U-M Head and Neck Oncology Program showed Bcl-xL protein is often highly expressed in head and neck cancers.

In this study, researchers developed head and neck cancer cell cultures resistant to the chemotherapy drug cisplatin, a platinum-based drug frequently used to treat this type of cancer. They found cisplatin killed cells with a mutant form of the protein p53, but cells with normal p53 and high levels of Bcl-xL were resistant. The researchers then treated these cisplatin-resistant cell lines with (-)-gossypol and found that (-)-gossypol induced the drug resistant tumor cells to undergo programmed cell death.

"These cisplatin resistant cells are exquisitely sensitive to (-)-gossypol. We can induce cell death in 70 percent to 90 percent of cells. This is a very impressive induction of cell death. It’s because we are targeting the pathways these cells need to survive," says Thomas Carey, Ph.D., co-director of the Head and Neck Oncology Program at the U-M Comprehensive Cancer Center and a professor in the U-M School of Dentistry and the U-M Medical School.

To test the principle that Bcl-xL and non-mutant p53 determine resistance to cisplatin in head and neck cancer cells, Joshua Bauer, a U-M graduate student in pharmacology, overexpressed Bcl-xL in tumor cells with mutant or non-mutant p53. Only cells with non-mutant p53 and high Bcl-xL became resistant to cisplatin. Bauer then treated these cells with (-)-gossypol and induced cell death. To further confirm the importance of Bcl-xL in cisplatin resistance, the researchers used a technique called inhibitory RNA to shut off expression of Bcl-xL in the drug-resistant cells. These cells became sensitive to cisplatin when Bcl-xL was turned off, confirming its role in drug resistance.

"We believe novel agents that target Bcl-xL can improve survival for our patients," Carey says. A prior study by the U-M Head and Neck Oncology Program showed that Bcl-xL protein is highly expressed in the majority of advanced head and neck cancers.

In a study published in November 2004 in Clinical Cancer Research, Bradford, Carey and their team treated cell cultures of head and neck squamous cell carcinoma with the (-)-gossypol compound and found it inhibited tumor cell growth. Additional testing in animals was also positive and showed (-)-gossypol did not harm surrounding healthy tissue. Researchers hope to begin a clinical trial within a year, testing whether (-)-gossypol can be used along with chemotherapy to create a better response and avoid surgery.

More than 29,000 people will be diagnosed in 2005 with head and neck cancers, which include cancer of the tongue, mouth, throat and voice box.

Gossypol is derived from cottonseed oil and was once used in China as a male contraceptive. The University of Michigan holds a patent on the negative isomer, (-)-gossypol, and has licensed the technology to Ascenta Therapeutics of San Diego, Calif., for commercial development. Wang is one of three U-M Medical School faculty members who founded the company and has significant financial interest.

Nicole Fawcett | EurekAlert!
Further information:
http://www.umich.edu
http://www.cancer.med.umich.edu/clinic/headneckclinic.htm.

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>