Novel Phosphonium Salt Derivatives Induce DNA Damage and Apoptosis in Cervical Cancer Cells

This study demonstrates that (Z)-(2-(2-hydroxy-5-chlorophenyl)-2-phenylethenyl)alkyldiphenylphosphonium chlorides exhibit high antitumour activity, comparable to that of the reference drug doxorubicin. The phosphonium salts exhibited reduced toxicity towards conditionally normal cell lines in the majority of cases. The mechanism of action of compound PP8, which contains an octyl radical at the phosphorus atom, on the model cell line M-HeLa included partial cell cycle arrest in the G1 phase, an increased generation of reactive oxygen species, and an induction of mitochondrial apoptosis. These experimental data are supported by the elevated levels of p53, p21, H2A.X and caspase-9 proteins detected by multiplex analysis. The results indicated the occurrence of double-strand DNA breaks under the influence of the studied compound. Therefore, additional structural modifications to enhance the selectivity of the studied compounds will provide a basis for the development of novel effective antitumour agents.