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 Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Foods of the future
15.08.2018 | Georg-August-Universität Göttingen

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: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

A novel synthetic antibody enables conditional “protein knockdown” in vertebrates

20.08.2018 | Life Sciences

Metamolds: Molding a mold

20.08.2018 | Information Technology

It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

20.08.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>