2-O-Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage-induced abnormal spindle...

Area of Science:

• Cell Biology
• Molecular Biology
• Tissue Homeostasis

Background:

• Spindle orientation is vital for maintaining tissue homeostasis and preventing aberrant growth.
• Spindle misorientation, often caused by caspase-3 activation producing N-terminal-deleted Rho guanine nucleotide dissociation inhibitor β (RhoGDIβ), disrupts tissue integrity and promotes abnormal repair.
• Targeting RhoGDIβ offers a therapeutic strategy for conditions involving spindle orientation abnormalities.

Purpose of the Study:

• To screen and identify chemical compounds that suppress RhoGDIβ expression.
• To investigate the potential of ascorbic acid (AA) derivatives for regulating spindle orientation.
• To find novel inhibitors of RhoGDIβ for therapeutic applications.

Main Methods:

• Screening of ascorbic acid (AA) derivatives for their ability to suppress RhoGDIβ expression in HeLa cells.
• Evaluation of the identified compounds for their effect on ionizing radiation-induced spindle misorientation.
• Assessment of antioxidant properties and specificity of inhibition.

Main Results:

• 2-O-octadecylascorbic acid (2-OctadecylAA), a lipophilic AA derivative, was identified as a novel RhoGDIβ inhibitor.
• 2-OctadecylAA specifically suppressed RhoGDIβ expression and ameliorated ionizing radiation-induced abnormal spindle orientations.
• The inhibitory activity of 2-OctadecylAA was distinct from its antioxidant properties.

Conclusions:

• 2-OctadecylAA effectively inhibits RhoGDIβ, suggesting a mechanism for its previously observed anticarcinogenic effects.
• Targeting RhoGDIβ with compounds like 2-OctadecylAA can attenuate spindle orientation perturbations.
• RhoGDIβ is a promising molecular target for treating epithelial homeostasis disorders caused by spindle misorientation.