Cancer has many causes, including inherited genes, alcohol and tobacco-use, and environmental carcinogens.
But scientists are now focusing more on viruses, such as Epstein-Barr virus (EBV), which have been linked to certain cancers, including diffuse large B cell lymphoma, Burkitt lymphoma, NK/T cell lymphomas, and Hodgkin lymphoma.
EBV is one of the most common viruses in the world. While it usually stays inactive, scientists have discovered that it can interfere with the immune system and how cells grow, sometimes leading to cancer. Cancers linked to EBV can be aggressive and may not respond well to standard treatments like chemotherapy, making it harder for doctors to treat patients.
A new study, published in Blood and led by researchers at the UNC School of Medicine and UNC Lineberger Comprehensive Cancer Center, offers a new and promising solution for EBV-positive cancer. The first-of-its-kind comprehensive analysis demonstrated that withaferin A-a chemical derived from the Ashwagandha plant-reduces tumor size, decreases the amount of virus, and improves survival in biological models.
"These findings establish withaferin A as a potent preclinical candidate that selectively targets vulnerabilities unique to EBV-transformed B cells, supporting further optimization and evaluation," said Jessica Stewart, PhD, a postdoctoral researcher in the lab of Blossom Damania, PhD, distinguished professor of microbiology and immunology at the UNC School of Medicine.
Blossom Damania, PhD
Medicinal plants have long served as bases for modern drug development. Stewart and Damania selected withaferin A (WA), a chemical derived from ashwagandha (Withania somnifera), as a therapy of interest due to its potent anti-cancer and anti-inflammatory properties.
The study revealed that WA disrupts viral and host survival pathways that allow cancer cells to grow and spread. In different biological models with EBV-driven cancer, Damania and Stewart found that WA:
- Prevented EBV from turning normal B cells into cancerous cells
- Targeted EBV-infected B cells over uninfected healthy B cells
- Reduced splenomegaly (a common symptom of B-cell cancer that leads to an enlarged spleen)
- Decreased the amount of tumors
- Significantly improved survival
What's more: WA's can breakdown EBNA1, a virus-encoded protein that is expressed across all EBV-driven cancers. This ability makes WA different from other lymphoma therapies, such as bortezomib, carfilzomib, and ixacomib, which do not degrade EBNA1.
With all this newfound information, Damania and Stewart are planning to conduct further studies to enhance the efficacy of WA, address partial resistance against WA, and advance WA or other compounds with similar molecular structures into early-phase clinical testing.
This study was supported by funding from National Institutes of Health.
