Mushroom compound appears to improve effectiveness of cancer drugs

October 11, 2011

AUGUSTA, Ga. - A compound isolated from a wild, poisonous mushroom growing in a Southwest China forest appears to help a cancer killing drug fulfill its promise, researchers report.

The compound, verticillin A, sensitizes cancer cells to TRAIL, a drug which induces cancer cells to self destruct, said Dr. Kebin Liu, cancer immunologist at the Georgia Health Sciences University Cancer Center and corresponding author of the study in the journal Cancer Research.

The compound appears to keep cancer cells from developing resistance to TRAIL, short for tumor necrosis factor-related apoptosis inducing ligand. Drug resistance, intrinsic or acquired, is a major problem for cancer patients, accounting for greater than 90 percent of treatment failures in patients with metastatic disease.

"If we can make drugs work again, more people will survive," Liu said.

Patient experience has shown cancer's skill at desensitizing itself to the TRAIL. "It looks as though most cancer cells have found a way to become resistant and evade its action," said Dr. Wendy Bollag, cell physiologist at GHSU and a study co-author. Tenacious cancer cells also are naturally resistant to cell suicide, which is how TRAIL works.

In mice, they found verticillin A alone was adequate to kill cancer cells, but the required dose made the mice sick, a common problem with many cancer therapies. However, when a lower dose was paired with TRAIL, it became a powerful, more tolerable recipe that killed previously resistant cells.

They also found that the compound improved the efficacy of commonly used cancer drugs etoposide and cisplatin, which also work by promoting cancer cell death but are less targeted than TRAIL. "We believe this could be a good companion drug for a lot of cancer therapies," Liu said.

One way verticillin A appears to work is by upregulating BN1P3, a gene that promotes cell death, the researchers said. Cancer cells work to silence BN1P3 through a process called DNA methylation; verticillin A appears to modify the same process to turn the gene on.

All cells use DNA methylation but cancer cells use it differently, said Dr. Keith Robertson, cancer epigeneticist and Georgia Cancer Coalition Scholar. "Verticillin A may be working by altering methylation in a way that makes the cancer cells sensitive to TRAIL," Robertson said.

Their studies were of metastatic human colon cancer cells, which are highly resistant to treatment, including TRAIL, both in culture as well as transplanted into mice. They did similar studies on sarcoma, lung adenocarcinoma and breast cancer.

Additional toxicity studies are needed before moving forward with clinical trials, Bollag said. The researchers also want to pursue the compound's potential in melanoma and pancreatic cancer.

Verticillin A was isolated from mushrooms in Dr. Ping Wu's laboratory at the Research Centre of Siyuan Natural Pharmacy and Biotoxicology at China's Zhejiang University and brought to GHSU by former postdoctoral fellow, Dr. Feiyan Liu, the study's first author, who studied with Kebin Liu in Augusta for two years. The Chinese university is involved in extensive studies to isolate active compounds from plants to explore their therapeutic potential and both Dr. Lius liked verticillin A's aggressive response against cancer.
-end-
GHSU and Zhejiang University have a joint use patent on verticillin A and Zhejiang University has a synthesis patent.

Medical College of Georgia at Augusta University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.