Navigation Links
Compound from Chinese medicine shows promise in head and neck cancer

A compound derived from cottonseed 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 appear in the July issue of the journal Molecular Cancer Therapeutics, 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 affects how you talk, how you swallow and how you breathe," says study author 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 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 ca ncer 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 study author 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, lead study author 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.

In a previous 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 in head and neck cancer patients 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.

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.


'"/>

Source:University of Michigan Health System


Related biology news :

1. First-ever Compounds To Target Only Metastatic Cells Are Highly Effective Against Breast, Prostate, And Colon Cancers
2. Newly Discovered Compound Blocks Known Cancer-Causing Protein
3. Compounds in plastic packaging act as environmental estrogens altering breast genes
4. Compound might defeat African sleeping sickness, clinical trial beginning this month
5. Anti-cancer Compound In Beer Gaining Interest
6. Compound from marine bacteria shows potential as multiple myeloma therapy
7. Compound in dairy products targets diabetes
8. Compound eyes, evolutionary ties
9. Rare Chinese frogs communicate by means of ultrasonic sound
10. Traditional Chinese medicine for diabetes has scientific backing
11. Active ingredient in common Chinese herb shown to reduce hypertension
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/6/2017)... , March 6, 2017 Mintigo ... technology, today announced Predictive Sales Coach TM , ... actionable sales intelligence into Salesforce. This unique AI ... their sales organizations with deep knowledge of their ... for intelligent engagement. Predictive Sales Coach extends Mintigo,s ...
(Date:3/2/2017)... 2017 Australian stem cell and regenerative medicine ... signed an agreement with the Monash Lung Biology Network, ... Institute and Department of Pharmacology at Monash University, ... study to support the use of Cymerus™ mesenchymal stem ... Asthma is a chronic, long term lung condition ...
(Date:2/28/2017)... , Spanien, 27. Februar 2017  EyeLock LLC, ein ... wird seine erstklassige biometrische Lösung zur Iris-Erkennung ... mit X16 LTE auf dem Mobile World ... am Qualcomm-Stand in Halle 3, Stand 3E10, ... die Sicherheitsplattform Qualcomm Haven™ – eine Kombination ...
Breaking Biology News(10 mins):
(Date:3/23/2017)... Research and Markets has announced the addition of ... offering. ... The Global Market for Bioproducts Should Reach $714.6 Billion ... of 8.9%, This research report quantifies the ... product segments: bio-derived chemicals, biofuels, pharmaceuticals (biodrugs and herbal/botanicals), biocomposite ...
(Date:3/23/2017)... 23, 2017  SeraCare Life Sciences, Inc., a ... vitro diagnostics manufacturers and clinical laboratories, is ... multiplexed Inherited Cancer reference material ... next-generation sequencing (NGS). The Seraseq™ Inherited Cancer DNA ... from industry experts to validate the ability ...
(Date:3/23/2017)... March 23, 2017  BioPharmX Corporation (NYSE MKT: ... the dermatology market, today reported financial results for ... and will provide an update on the company,s ... "We are pleased to report that ... BioPharmX," said President Anja Krammer. "We achieved key ...
(Date:3/23/2017)... , March 23, 2017 Kineta, Inc., ... of novel therapies in immuno-oncology, today announced the ... small molecule compounds that activate interferon response factor ... and demonstrate immune-mediated tumor regression in a murine ... study who demonstrated complete tumor regression to initial ...
Breaking Biology Technology: