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 sile
|Contact: Toni Baker|
Georgia Health Sciences University