The novel antitumor compound P8-D6 promotes apoptosis by acting as dual topoisomerase inhibitor

Introduction Breast cancer (BC) is the most lethal malignancy diagnosed in women worldwide. Hence, development of novel drugs with higher efficacy, lower resistance potential and fewer side effects is still a clinical need in a successful BC therapy. The new effective inductor of apoptosis P8-D6 acts as a dual topoisomerase poison by stabilizing the covalent Topo-DNA-intermediate of both topoisomerase enzymes I and II. The present study outlines a strong antitumor effect of P8-D6 in BC.

Methods This study provides an overview of the effectiveness of P8-D6 in great detail by looking at its effects in 2D monolayers, 3D culture, and in a translational approach in primary BC cells established ex vivo. The main parameters to quantify the effect of P8-D6 were including cytotoxicity, apoptosis rate and membrane integrity. Likewise, the effects on non-cancer cells were analysed and hepatotoxicity was investigated.

Results This study provides evidence for a significant P8-D6-induced increase in apoptosis and cytotoxicity in breast cancer cells compared to the efficacy of standard therapeutic drugs. Non-cancer cells were slightly effected and no hepatotoxic effect in vitro was detectable.

Conclusion This present study outlines the outstanding apoptotic effect of P8-D6 in breast cancer cell lines and in a translational approach in ex vivo BC primary patient cells both in 2D monolayers and 3D culture compared to standard therapeutics. In order to prove the benefit of P8-D6 treatment for BC therapy in multiorgan systems and to verify potential toxic or side effects, further in vivo experiments would be beneficial.

Publication History

Article published online:
21 June 2022