Chemoresistance and limited broad-spectrum efficacy remain major challenges in cancer therapy. The development of agents capable of overcoming resistance and exhibiting activity across diverse tumour types is therefore critical to improving treatment outcomes. Here, we demonstrate the antiproliferative activity of a steroidal-nitroxide hybrid across multiple cell lines. CS187 , a first-generation hybrid identified from previous work in cervical cancer, exhibited concentration-dependent antiproliferative activity with associated morphological changes in prostate (C4–2B), breast (MCF-7), and lung cancer (H460 and A549) cells at concentrations of 11–50 µM. In-combination with cisplatin, CS187 potentiated antiproliferative effects, achieving comparable growth inhibition at reduced cisplatin doses. Assessment of reactive oxygen species (ROS) levels revealed that CS187 , both alone and in-combination with cisplatin, induced sustained intracellular oxidative stress, whereas cisplatin monotherapy exhibited attenuation over the time course. Together, these findings suggest that CS187 acts predominantly through a cytostatic mechanism and may interfere with redox-mediated adaptive responses that typically limit cisplatin efficacy. This work identifies CS187 as a promising redox-modulating scaffold capable of enhancing chemotherapeutic efficacy while potentially enabling dose reduction across multiple cancer types. • Hybrid CS187 exhibits anti-proliferative activity in multiple cell lines. • The hybrid structure is necessary for the observed anti-proliferative activity. • The findings suggest CS187 induces predominantly cytostatic effects. • CS187 -cisplatin combination improves efficacy, enabling reduced cisplatin doses. • CS187 disrupts redox adaptation to cisplatin, sustaining ROS elevation.
Soltau et al. (Sat,) studied this question.