Antiproliferative activity in breast cancer cells of PtL₂: A steroid-thiosemicarbazone platinum(II) complex

Breast cancer remains one of the most diagnosed cancers in women worldwide. Metallodrugs such as cisplatin are used in advanced stages and hormone independent tumors. We hereby report the synthesis and characterization of a new benzaldehyde thiosemicarbazone functionalized with an estradiol derivative, LH, and two metal complexes, PdCl₂(LH) and PtL₂. Both complexes were studied in solution showing enough stability to further perform antitumoral activity studies. The Pd(II) complex was discarded for its poor performance while PtL₂ exhibited similar cytotoxic activity to cisplatin (CDDP) in estrogen receptor (+) and triple-negative breast cancer cells. Moreover, PtL₂ demonstrated reduced toxicity in healthy cell lines. It induced cell cycle arrest at the G0/G1 phase, distinguishing its mechanism of action from CDDP, which predominantly blocks cells in the S phase. Additionally, PtL₂ displayed a balanced intracellular distribution between the nucleus and cytoplasm, independent of estrogen receptor status. Further analysis revealed that PtL₂ dysregulated antioxidant enzyme expression, potentially disrupting redox homeostasis. These findings highlight PtL₂'s potential as a promising alternative to conventional platinum-based therapies, warranting further investigation into its molecular mechanisms and therapeutic applications.