Blood Cancer Combatants

By Travis Rains
Dr. Subbarao Bondada and his team of University of Kentucky graduate students, in partnership with Dr. Ramesh Gupta of the University of Louisville, are hoping to find a future treatment for blood cancers by studying a remedy that has existed for thousands of years.
The herbal remedy extracted from the Winter Cherry plant, or Withania Somnifera has already been shown to have some impact on other cancers but until now its effect on blood cancers has been largely unstudied. “The novelty of our study is suggesting that Withaferin A inhibits the B cell receptor signaling pathway in B lymphoma cells which is required for survival,” said Katie McKenna, a UK graduate student and member of Bondada’s team. Non-Hodgkin Lymphoma, the target of the study, is a type of blood cancer which is derived from the before mentioned B cells, and accounts for 4.3% of new cancer cases. In laymen terms, Withaferin A destroys B lymphoma cells by by cutting them off from the signaling pathway needed for survival, and prevents downstream activation markers inside the B cells.
McKenna said that the medicinal history of Withania Somnifera goes back thousands of years in India, to the practice of Ayurvedic medicine. The historical uses of the Winter Cherry plant reflects the philosophy of Ayurvedic medicine, which focuses on the importance of a healthy balance between mind, body and spirit.
While Withaferin A is now being studied as a way to combat cancers,it has long been used as a rejuvenating herbal drug, an anti-inflammatory and was once thought to promote longevity, learning and memory.
McKenna said the change in focus came as a result of some promising preclinical studies that showed Withaferin A having a potent, “anti-cancer activity in a variety of solid tumors that include breast, prostate, pancreatic, lung, colon, melanoma and cervical cancers.” The studies also showed that the extract, in combination with other cancer-fighting drugs (known technically as chemotherapeutic agents) seem to help lower overall doses and toxicity levels of chemotherapy.
Bondada and his students are trying to determine whether Withaferin A will also fight malignancies in B-cells, a type of white blood cell, McKenna said. What piqued the researchers interest in this possibility was was a study done earlier by Yu et al from the University of Michigan on how Withaferin A inhibited cancer-enhancing proteins in pancreatic cancer. McKenna said that this same protein activity is present in B-cell lymphomas, the focus of their studies. Previous research by the lab showed promising results, McKenna said, but there is still a lot of work to determine the mechanism of how the drug kills malignant B cells.
While the study has been going on since 2012, up to now their lab has been busy with these preliminary tests on cancer cell lines, primary cells and mouse models. However, McKenna noted that the job is not done and more work is required to further define the mechanism. Bondada and his team are now trying to determine whether Withaferin A will also fight chronic lymphocytic leukemia, another type of malignancy found in B Cells, McKenna said.
The work being done by Bondada and his team is only possible with the help of U of L’s Gupta, who provides Withaferin A compound purified from the Winter Cherry plant extract.
“Our collaboration opens discussion to explore different ways to enhance a project and look at it from different viewpoints,” said McKenna. This spirit of collaboration and teamwork is reflected in a statement by Bondada. He notes that the study is a result of hard work by Gupta, himself, his lab manager, Ms. Gachuki. and his team of graduate students Ms. McKenna, Ms. Alhakeem and Ms. Oben.
When asked about the next phase of their work, McKenna was optimistic. “Many further studies must be completed in order to reach these goals, but the results are promising.”