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Cell culture studies of xanthopterin and isoxanthopterin
Xanthopterin and isoxanthopterin are naturally occurring compounds found in humans and other species. Evidence in cell-based and lab animal experimental systems suggests they may play a role in reducing the growth of cancer cells. The objectives of this study were to determine cytotoxicity potential of xanthopterin and isoxanthopterin in Jurkat cells, an immortalized human T-cell line, and to test the anti-inflammatory effects of both chemicals in RAW264.7 cells. Cell viability was tested using the MTT assay as a measure of mitochondria activity at 48 hours exposure to pterins with concentration ranges of 0-200 µM. Xanthopterin had cytotoxic effects on the Jurkat cells, showing an IC50 concentration of approximately 69 µM. Isoxanthopterin showed no significant loss of viability at 50-200 mM in Jurkat cells. Although these two pterin compounds have identical molecular weights and are very similar in structure, there is a difference in cytotoxic properties of these two compounds in Jurkat cells for reasons that remain unknown and warrant future study. Antiinflammatory effects were evaluated using the Griess assay with concentration ranges of 5-90 µM. Both compounds showed a virtually identical dose response inhibition of nitric oxide (NO) production in RAW264.7 cells. It can be concluded that xanthopterin and isoxanthopterin both have anti-inflammatory effects, Xanthopterin had an IC50 of around 33 µM and isoxanthopterin had an IC50 of about 37.5 µM. There was no significant toxicity to the RAW264.7 cells from either compound even at 90 µM when evaluated using the MTT assay. IC50 values and cytotoxic response in Jurkat cells is consistent with other studies that show similar cytotoxic effects of isoxanthopterin and xanthopterin in Jurkat cell lines. In Jurkat cells nitric oxide functions as a chemical mediator that inhibits apoptosis. Further studies of anti-inflammatory properties in Jurkat and other human cell lines are suggested, including determining whether these two pterins preferentially affect different cell types, and whether the mechanism of inhibition involves decreased NO production or scavenging of the NO produced. It would also be valuable to follow up on the idea that the xanthopterin-related increased apoptosis in Jurkat cells previously reported could be mechanistically related to its anti-inflammatory properties.
Health and Human Services
Master of Science (M.S.) San Diego State University, 2011
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