%0 Journal Article
%T Cytotoxicity and cell cycle changes in prostate cancer cells with differing PSMA expression and p53 status after treatment with PSMA-targeting radioligand [212Pb]Pb-AB001
%W https://pubmed.ncbi.nlm.nih.gov/41318731/
%* 2025 The Author(s)
%U https://www.nature.com/articles/s41598-025-29785-7
%X Targeted alpha therapy holds promise for treating advanced prostate cancer, but the interplay between prostate-specific membrane antigen (PSMA) expression, p53 status, and downstream cell fate remains poorly defined. This study evaluates the cytotoxic and cell cycle effects of the alpha-emitting radioligand [212Pb]Pb-AB001 in prostate cancer cell lines with differing PSMA expression and p53 status: C4-2 (PSMA+/TP53-wild-type) and PC-3 PIP (PSMA+++/ TP53-null). [212Pb]Pb-AB001 significantly inhibited proliferation and clonogenic survival in both cell lines in an activity-dependent manner. At 95% clonogenic inhibition, both cell lines exhibited G2-phase arrest, S-phase suppression and reduced mitotic entry on day 1. At higher activities, PC-3 PIP cells showed polyploidy, and features consistent with mitotic catastrophe and senescence. Cytotoxicity was more pronounced in C4-2 3D spheroid models than in 2D monolayers, suggesting contribution of crossfire and bystander effects. Total cell-bound activity, rather than added activity, better predicted radiotoxicity in both TP53-wild-type and TP53-null cell lines, indicating that its therapeutic effect is primarily governed by PSMA-mediated uptake rather than p53 status. These results support the therapeutic potential of [212Pb]Pb-AB001 across cells with varying TP53 status and suggest that combining [212Pb]Pb-AB001 with DNA repair or checkpoint inhibitors may enhance treatment efficacy.
%G en
%J Scientific Reports
%A Stenberg, Vilde Yuli
%A Liukaityte, Rugile
%A Kristiansen, Sandra Kvarsvik
%A Wangen-Riise, Rina
%A Kleinauskas, Andrius
%A Dunne, Victoria
%A Juzeniene, Asta
%D 2025-11-29
%K Cancer
Cell biology
Oncology
scientific-publication