According to study published in the journal Cancer Research, wild, poisonous mushrooms growing in a Southwest China forest carry a compound that seems to be effective in helping a cancer killing drug live up to its promise.
Dr. Kebin Liu, cancer immunologist at the Georgia Health Sciences University Cancer Center and corresponding author, explained: “The compound, verticillin A, sensitizes cancer cells to TRAIL, a drug which induces cancer cells to self destruct.”
It appears that verticillin A prevents cancerous cells from developing resistance to TRAIL (tumor necrosis factor-related apoptosis inducing ligand). A major problem for cancer sufferers is acquired or intrinsic drug resistance, which accounts for more than 90% of failed treatments in individuals with metastatic disease.
Liu said: “If we can make drugs work again, more people will survive.”
Patient experience has revealed the skill in which cancer can desensitize itself to the TRAIL. Dr. Wendy Bollag, cell physiologist at GHSU and co-author of the study, explained: “It looks as though most cancer cells have found a way to become resistant and evade its action.” By nature tenacious cancer cells are also resistance to cell suicide, which is how TRAIL works.
They discovered that in mice, the compound alone was enough to destroy cancer cells, however, the dose required made the mice sick, which is a common issue with several cancer treatments. Though, when a lower dose of verticillin A was combined with TRAIL, they found it became more tolerable and powerful and killed cells that were previously resistant.
In addition, the researchers found that verticillin A improved the effectiveness of etoposide and cisplatin, commonly used cancer medications which are less targeted than TRAIL, but that also work by encouraging cell suicide. Liu explained: “We believe this could be a good companion drug for a lot of cancer therapies.”
According to the researchers, one method in which verticillin A seems to work is by upregulating BN1P3, a gene that promotes cell death. Through a method called DNA methylation, cancer cells try to silence BN1P3, however, it seems that verticillin A alters the same method in order to activate the gene.
Dr. Keith Robertson, cancer epigeneticist and Georgia Cancer Coalition Scholar, said:
“All cells use DNA methylation but cancer cells use it differently. Verticillin A may be working by altering methylation in a way that makes the cancer cells sensitive to TRAIL.”
The investigation from the researchers involved metastatic human colon cancer cells, which including TRAIL, are highly resistant to treatment, in both culture and when transplanted into mice. They also carried out similar investigations on breast, lung adenocarcinoma, and sarcoma cancer.
Bollag explained: “Additional toxicity studies are needed before moving forward with clinical trials.” The investigators are also keen to test the potential of verticillin A in pancreatic and melanoma 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 investigation’s initial author, who along with Kebin Liu studied in Augusta for two years. The Chinese university is involved in extensive investigations to isolate active compounds from plants to examine their therapeutic potential and both Dr. Lius liked verticillin A’s aggressive response against cancer.
GHSU and Zhejiang University have a joint use patent on verticillin A and Zhejiang University has a synthesis patent.
Written by Grace Rattue