Targeting mitochondrial translation by inhibiting DDX3 : A novel radiosensitization strategy for cancer treatment

DDX3 is a DEAD box RNA helicase with oncogenic properties. RK-33 is developed as a small-molecule inhibitor of DDX3 and showed potent radiosensitizing activity in preclinical tumor models. This study aimed to assess DDX3 as a target in breast cancer and to elucidate how RK-33 exerts its anti-neoplastic effects. High DDX3 expression was present in 35% of breast cancer patient samples and correlated with markers of aggressiveness and shorter survival. With a quantitative proteomics approach, we identified proteins involved in the mitochondrial translation and respiratory electron transport pathways to be significantly downregulated after RK-33 or DDX3 knockdown. DDX3 localized to the mitochondria and DDX3 inhibition with RK-33 reduced mitochondrial translation. As a consequence, oxygen consumption rates and intracellular ATP concentrations decreased and reactive oxygen species (ROS) increased. RK-33 antagonized the increase in oxygen consumption and ATP production observed after exposure to ionizing radiation and reduced DNA repair. Overall, we conclude that DDX3 inhibition with RK-33 causes radiosensitization in breast cancer through inhibition of mitochondrial translation, which results in reduced oxidative phosphorylation capacity and increased ROS levels, culminating in a bioenergetic catastrophe

Morality Politics and Prostitution Policy in Brussels: A Diachronic Comparison

Abstract: This paper discusses the genealogy of prostitution policies in Brussels through the lens of morality politics. It uses the analytical framework proposed by Hendrik Wagenaar and Altink (2012) to compare the formulation and implementation of policies in the nineteenth and early twentieth centuries with today's policymaking in Brussels as well as the discourses underlying those policies. Although it departs from the six characteristics of morality politics, the study introduces one element that adds to the complexity of policymaking in this domain: gender. We argue that a gendered ideology and stigma have informed past and present prostitution policies in Brussels and that the many actors involved in the city's policymaking have more often than not relied on emotions and personal views on female sexuality to support their calls for the control or outright repression of public commercial sex. The comparative analysis illustrates the persistent symbolic nature of policy formulation and a blatant disregard for data, both of which have led to the approval of unworkable laws and sudden policy shifts. However, the participation of new actors in the debates about prostitution in recent years has ushered in an increase in questionings of morality politics and will hopefully bolster calls for fact-based policies