Search

The NF-E2-related factor 2 transcription factor (Nrf2) orchestrates the basal and stress-inducible activation of a vast array of antioxidant genes. A high amount of reactive oxygen species (ROS) promotes carcinogenesis in cells with defective redox-sensitive signaling factors such as Nrf2. In breast cancer (BC), emerging evidence indicates that increased Nrf2 activity enhances cell metastatic potential. An interconnection between peroxisome proliferator-activated receptors (PPARs) and Nrf2 pathways in cancer has been shown. In this light, newly synthesized PPARα antagonists, namely IB42, IB44, and IB66, were tested in the BC cell line MCF7 in parallel with GW6471 as the reference compound. Our results show that the most promising compound of this phenylsulfonimide series (IB66) is able to decrease MCF7 proliferation by blocking cells at the G2/M checkpoint. The underlying mechanism has been investigated, disclosing a caspase 3/Akt-dependent apoptotic/pyroptotic pathway induced by the increased generation of oxidative stress. Moreover, the involvement of Nrf2 and COX2 in IB66-treated MCF7 cell response has been highlighted. The reported data lay the groundwork for the development of alternative targeted therapy involving the Nrf2/PPARα molecular axis, able to overcome BC cell chemoresistance and cause better clinical outcomes, promoting other forms of programmed cell death, such as pyroptosis.

In the last decade, many innovative nanodrugs have been developed, as well as many nanoradiocompounds that show amazing features in nuclear imaging and/or radiometabolic therapy. Their potential uses offer a wide range of possibilities. It can be possible to develop nondimensional systems of existing radiopharmaceuticals or build engineered systems that combine a nanoparticle with the radiopharmaceutical, a tracer, and a target molecule, and still develop selective nanodetection systems. This review focuses on recent advances regarding the use of gold nanoparticles and nanorods in nuclear medicine. The up-to-date advancements will be shown concerning preparations with special attention on the dimensions and functionalizations that are most used to attain an enhanced performance of gold engineered nanomaterials. Many ideas are offered regarding recent in vitro and in vivo studies. Finally, the recent clinical trials and applications are discussed.