Biomedical Chemistry: Research and Methods 2025, 8(1), e00254

NOVEL PHOSPHONIUM SALT DERIVATIVES INDUCE DNA DAMAGE AND APOPTOSIS IN CERVICAL CANCER CELLS

A.P. Lyubina*, A.D. Voloshina, S.K. Amerkhanova, A.S. Sapunova, D.A. Tatarinov, V.F. Mironov

Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, 8 Arbuzov str., Kazan, 420088 Russia; *e-mail: aplyubina@gmail.com

Keywords: phosphonium salts; apoptosis; DNA damage; cell cycle

DOI:10.18097/BMCRM00254

The whole version of this paper is available in Russian.

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.
Figure 1. Changes in the adhesive properties of M-HeLa and Chang liver cells in a real-time experiment when exposed to different concentrations of the PP8 compound.

Figure 2. Effect of compound PP8 on the cell cycle of M-HeLa and Chang liver cells.* - p<0.01 when compared with the control sample.

Figure 3. Multiplex analysis of DNA damage/genotoxicity markers in M-HeLa cells after exposure to compound PP8. * - p<0.01 when compared with the control sample.

Figure 4. Induction of apoptosis in M-HeLa and Chang liver cells in the presence of compound PP8. A – living cells, B – cells at the stage of early apoptosis, C – cells at the stage of late apoptosis, D – dead cells.

Figure 5. Changes in mitochondrial membrane potential in M-HeLa and Chang liver in the presence of compound PP8.

Figure 6. Multiplex analysis of early apoptosis markers in M-HeLa cells after exposure to compound PP8. * - p<0.01 when compared with the control sample.

Figure 7. ROS level in M-HeLa and Chang liver cells in the presence of compound PP8; * - p<0.01 when compared with the control sample.

CLOSE
Table 1. Cytotoxicity of the studied compounds against human cell lines of various origins.

CLOSE
Table 2. Selectivity index (SI) of the studied compounds, calculated in relation to IC50 in conditionally normal Chang liver and RPMI 1788 cells.

FUNDING

The work was carried out within the framework of the state assignment of the FRC Kazan Scientific Center of RAS.

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