Erxi Wu, assistant professor of pharmaceutical sciences, and Fengfei Wang, research associate of pharmaceutical sciences in the Wu lab, co-wrote the article, "Cambogin is preferentially cytotoxic to cells expressing PDGFR.” It will be published by PLoS ONE, an online journal that highlights original research from all disciplines within science and medicine.
According to the authors, platelet-derived growth factor receptors (PDGFRs) are linked to an array of human malignancies, including medulloblastoma, the most common brain tumor affecting children. Although significant progress in medulloblastoma biology and therapeutics has been achieved during the past decades, it remains a formidable challenge to physicians and researchers. Therefore, novel inhibitors targeting platelet-derived growth factor receptors signaling pathway may offer great promise for the treatment of medulloblastoma. In the current study, the researchers found that cambogin is preferentially cytotoxic to cells expressing platelet-derived growth factor receptors and investigated the mechanisms of cambogin in Daoy medulloblastoma cells.
“Cambogin was isolated from Garcinia cowa, a tropical subcanopy climax tree indigenous to monsoon rain forests in southwest Asia with cooling and detoxification functions. Our previous study has demonstrated that a xanthone derivate dulxanthone A isolated from G. Cowa induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells. Here, we show that cambogin triggers significant S phase cell cycle arrest and apoptosis via down regulation of cyclin A and E, and activation of caspases. More importantly, further mechanistic studies demonstrated that cambogin inhibits PDGFR signaling in Daoy and genetically defined mouse embryo fibroblast cell lines. Our findings may provide a novel approach by targeting PDGFR signaling against medulloblastoma,” senior author Wu said.
The first author for the paper is Ze Tian, Wu’s first postdoctoral research fellow, now a faculty member at Harvard Medical School. Other collaborators include Jie Shen, Peigen Xiao and Junshan Yang from Peking Union Medical College and Hetian Lei, Andrius Kazlauskas and Isaac Kohane from Harvard Medical School.
Part of the research received support from the Centers of Biomedical Research Excellence grant NIH P20 RR020151 from the National Center for Research Resources. Wu was offered a pilot project grant from the NDSU Center for Visual and Cognitive Neuroscience a few months ago. “I was happy to offer Dr. Wu a two-year pilot project based on his outstanding proposal submitted to compete for pilot project grants among NDSU faculty proposing research projects,” said Mark McCourt, Dale Hogoboom Professor of Psychology and Director of the Center for Visual and Cognitive Neuroscience at NDSU. “Dr. Wu has made very good use of the pilot project funding.”
“We are grateful for Dr. McCourt’s support, which will allow us to continue this exciting research on targeting diseases in which PDGFR is a therapeutic target such as PVR (proliferative vitreoretinopathy) and brain tumors,” Wu said.
To view the paper, visit www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0021370.