Organometallics, such as copper compounds, are cancer chemotherapeutics used alone or in combination with other drugs. One small group of copper complexes exerts an effective inhibitory action on topoisomerases, which participate in the regulation of DNA topology. Copper complexes inhibitors of topoisomerases 1 and 2 work by different molecular mechanisms, analyzed herein. They allow genesis of DNA breaks after the formation of a ternary complex, or act in a catalytic mode, often display DNA intercalative properties and ROS production, and sometimes display dual effects. These amplified actions have repercussions on the cell cycle checkpoints and death effectors. Copper complexes of topoisomerase inhibitors are analyzed in a broader synthetic view and in the context of cancer cell mutations. Finally, new emerging treatment aspects are depicted to encourage the expansion of this family of highly active anticancer drugs and to expend their use in clinical trials and future cancer therapy.
28 September 2001 in Molecular Reproduction and Development
Interleukins (ILs) are known best for their involvement in the immune system and their role during inflammation. In the ovary, a growing body of evidence suggests that the ovarian follicle is a site of inflammatory reactions. Thus ovarian cells could represent sources and targets of ILs. Since then, the IL-1 system components (IL-1alpha, IL-1beta, IL-1 receptor antagonist, IL-1 receptors) have been demonstrated to have several sites of synthesis in the ovary. These factors have been localized in the various ovarian cell types, such as the oocyte, granulosa and theca cells, in several mammalian species. IL-1-like bioactivity has been reported in human and porcine follicular fluid at the time of ovulation. The role of IL-1 in local processes is still poorly known, although there is evidence for involvement in the ovulation process, and in oocyte maturation. More precisely, IL-1 may be involved in several ovulation-associated events such as the synthesis of proteases, regulation of plasminogen activator activity, prostaglandin and nitric oxide production. IL-1 also regulates ovarian steroidogenesis. These different aspects of the involvement of the IL-1 system in important aspects of female reproduction are discussed.
Cells respond to genotoxic stress through a series of complex protein pathways called DNA damage response (DDR). These monitoring mechanisms ensure the maintenance and the transfer of a correct genome to daughter cells through a selection of DNA repair, cell cycle regulation, and programmed cell death processes. Canonical or non-canonical DDRs are highly organized and controlled to play crucial roles in genome stability and diversity. When altered or mutated, the proteins in these complex networks lead to many diseases that share common features, and to tumor formation. In recent years, technological advances have made it possible to benefit from the principles and mechanisms of DDR to target and eliminate cancer cells. These new types of treatments are adapted to the different types of tumor sensitivity and could benefit from a combination of therapies to ensure maximal efficiency.