The Effects of cAMP on the Invasion of Glioblastoma Neurospheres (2023)

Undergraduate: Elizabeth Redding

Faculty Advisor: Lauren Haar
Department: Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy

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Glioblastoma Multiforme (GBM) is a type of brain tumor that displays highly aggressive invasion, making surgical resection nearly impossible. A promising category of GBM therapeutic agents are activators of cyclic-mediated adenosine monophosphate (cAMP). cAMP, a type of second messenger, has been shown to have lower expression levels in many different types of cancer but the reason and mechanism of its downregulation is unknown. The compartmentalized functions of cAMP and the signaling that occurs in distinct microdomains make it a complicated pathway to study. Here, we describe the effects of cAMP activation on the growth and invasion of GBM neurospheres. The pharmaceutical treatment forskolin and the photoactivatable bPAC were used as methods of cAMP activation in MMK1 cells. Forskolin significantly decreased the growth and invasion of neurospheres in the presence and absence of bPAC, supporting the hypothesis that cAMP activation decreases GBM invasion. However, cells treated with bPAC as a means for activating cAMP did not show significant differences in growth or invasion. Future studies should continue to optimize the use of bPAC site-specifically, in order to localize the activation of cAMP.

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