Investigating the effects of myo-inositol phosphates on human cancer cells
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Date
2024
Authors
Witten, David J.
University of Lethbridge. Faculty of Arts and Science
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Publisher
Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry and Biochemistry
Abstract
In this thesis we investigate the effects of myo-inositol phosphates on human cancer cells. We determined that InsP6 and two InsP5 isomers, specifically Ins(2,3,4,5,6)P5 and Ins(1,2,4,5,6)P5, induce vesicle formation in the ER of two human cancer cell lines. We also determined that Ins(1,2,3,4)P4 did not induce vesicles in cells. We predict that the specificity of the vesicle phenotype is limited to higher-phosphorylated IPs. This is the first time either InsP5 isomer has been exogenously applied to cells in vitro. To our knowledge, we are also the first to report IP-mediated vesicle formation within the ER in any human cell line. Additionally, InsP6, Ins(1,2,4,5,6)P5 and Ins(2,3,4,5,6)P5 formed precipitate in cell culture media whereas Ins(1,2,3,4)P4 did not. Occurrence of IP precipitation in cell culture media is noted in the literature, yet little is known about the effect the precipitate has on cells itself. Despite observing that IP precipitation occurred simultaneously with the vesicle phenotype, we determined that the precipitate itself was not cause of vesicle formation. We also determined that vesicle formation was not due to extracellular cation depletion by the precipitate as EGTA and DFO could not induce a similar effect. The effects of InsP6 are relatively well characterized in vitro, yet its mechanism of action often remains ambiguous. Therefore, the novel discovery that InsP6 and two chemically related InsP5 isomers induce vesicle formation in the ER of human cancer cells offers new insights relevant to mechanistic discussion behind exogenous InsP6 effects, especially those already present in the literature.
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Keywords
vesicle formation , vacuole formation , precipitate , calcium , tissue culture , myo-inositol phosphates , endoplasmic reticulum