A group of NDSU researchers will have their paper on brain tumor cells published in the interdisciplinary journal, Current Molecular Medicine.
Erxi Wu, assistant professor of pharmaceutical sciences; Fengfei Wang, research associate of pharmaceutical sciences; Kruttika Bhat, doctoral student in Wu’s lab; Matthew Doucette, Pharm D. student; and Shuang Zhou, doctoral student in Wu’s lab, co-wrote, "Docosahexaenoic Acid (DHA) sensitizes brain tumor cells to etoposide-induced apoptosis.”
The group investigated whether the addition of DHA, a nutritionally important n-3 unsaturated fatty acid, modulated the sensitivity of brain tumor cells to the anticancer drug, etoposide (VP16). Medulloblastoma (MB) cell lines, Daoy and D283, and glioblastoma (GBM) cell lines, U138 and U87, were exposed to DHA or VP16 as single agents or in combination. The effects on cell proliferation and induction of apoptosis were determined by using MTS and Hoechest 33342/PI double staining. U87 and U138 cells were found to be refractory to addition of DHA and VP16 while the two MB cell lines showed high sensitivity. DHA or VP16 added alone showed little effect on cell proliferation or death in either MB or GBM cell lines while pretreatment with DHA enhanced responsiveness to VP16 in MB cell lines. To understand the mechanisms by which combined DHA and VP16 affected MB cells, pathway specific oligo array analyses were performed to dissect possible signaling pathways involved. Addition of DHA and VP16, in comparison to VP16 added alone, resulted in marked suppression in the expression of several genes involved in DNA damage repair, cell proliferation, survival, invasion and angiogenesis, including, respectively, PRKDC, Survivin, PIK3R1, MAPK14, NFkappaB1, NFkappaBIA, BCL2, CD44 and MAT1.
“These results suggest that effects of DHA and VP16 in brain tumor cells are mediated at least in part by down regulation of events involved in DNA repair and the PI3K/MAPK signaling pathways, and raise the possibility that brain tumors genotypically mimicked by MB cells may benefit from therapies combining VP16 with DHA,” said the senior author Wu. They have collaborated with Steven Qian and Benedict Law, assistant professors at NDSU. Other collaborators include Yan Gu, doctoral student in Qian’s lab; Xinli Liu, assistant professor at Texas Tech University Health Sciences Center; Eric Wong, associate professor at Harvard Medical School; Jing X. Kang, professor at Massachusetts General Hospital and Harvard Medical School; and Tze-chen Hsieh, research associate professor at New York Medical College.
Current Molecular Medicine is an interdisciplinary journal focused on providing current and comprehensive reviews and original research articles on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. Its current impact factor is 5.096, ranking 11th of 92 medicine, research and experimental journals, according to its website, www.benthamscience.com/cmm/index.htm.
Wu’s laboratory research interests include tumor therapeutic targets, drug discovery and biomarkers. Wu joined NDSU in December 2008. Prior to joining NDSU, Wu worked at Harvard University for more than 10 years. Wu was a faculty member at Children’s Hospital Boston, Harvard University. Concurrently, Wu has been a special professor at the Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing since 2007. Since he joined NDSU, his lab has published or submitted more than 20 manuscripts in high-tier journals.
