Compound from Chinese Medicine Shows Promise in Head and Neck Cancer
ANN ARBOR, Mich. - 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.