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Spindle misorientation due to imbalance or improper functioning leads to a loss of tissue integrity and aberrant growth, such as tissue loss or overgrowth. Pharmacological manipulation to prevent spindle misorientation will enable a better understanding of how spindle orientation is involved in physiological and pathological conditions and will provide therapeutic possibilities to treat patients associated with abnormal tissue function caused by spindle misorientation. N\u2010terminal\u2010deleted Rho guanine nucleotide dissociation inhibitor \u03b2 (RhoGDI\u03b2\/RhoGDI2\/LyGDI) produced by caspase\u20103 activation perturbs spindle orientation in surviving cells following exposure to either ionizing radiation or UVC. Thus, presumably, RhoGDI\u03b2 cleaved by caspase\u20103 activation acts as a determinant of radiation\u2010induced spindle misorientation that promote aberrant tissue repair due to deregulation of directional organization of cell population and therefore becomes a potential target of drugs to prevent such response. The objective of this study was to screen and identify chemicals that suppress RhoGDI\u03b2 expression. We focused our attention on ascorbic acid (AA) derivatives because of their impact on the maintenance of skin tissue homeostasis. Here, we screened for AA derivatives that suppress RhoGDI\u03b2 expression in HeLa cells and identified a lipophilic derivative, 2\u2010<jats:italic>O<\/jats:italic>\u2010octadecylascorbic acid (2\u2010OctadecylAA), as a novel RhoGDI\u03b2 inhibitor that ameliorated ionizing radiation\u2010induced abnormal spindle orientations. Among all examined AA derivatives, which were also antioxidative, the inhibition activity was specific to 2\u2010OctadecylAA. Therefore, this activity was not due to simple antioxidant properties. 2\u2010OctadecylAA was previously shown to prevent hepatocellular carcinoma development. Our findings suggest that the anticarcinogenic effects of 2\u2010OctadecylAA are partly due to RhoGDI\u03b2 inhibition mechanisms by which spindle orientation perturbations are attenuated. Thus, the molecular targeting features of RhoGDI\u03b2 warrant its further development for the treatment or control of spindle orientation abnormalities that affect epithelial homeostasis.<\/jats:p>","DOI":"10.1002\/jcb.29908","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T16:14:25Z","timestamp":1613578465000},"page":"739-751","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["2\u2010<i>O<\/i>\u2010Octadecylascorbic acid represses RhoGDI\u03b2 expression and ameliorates DNA damage\u2010induced abnormal spindle orientations"],"prefix":"10.1002","volume":"122","author":[{"given":"Natsumi","family":"Doi","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Faculty of Life and Environmental Sciences Prefectural University of Hiroshima  Hiroshima 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