Rivaroxaban Modulates Cervical Cancer Cell Growth via TRAP1, Bcl-2/Bcl-xL, and BAX-BAK: A Dual-Effect Study

Objective: This study examined the effect of rivaroxaban on cervical cancer growth and its tendency to target TRAP1, Bcl-2/Bcl-xL anti-apoptotic proteins, and BAK-BAX pro-apoptotic proteins.Methods: The study utilized an MTT assay to evaluate the impact of rivaroxaban on the proliferation of HeLa cervical cancer cells at 24 and 72 hours. Human fibroblast cells (HFF) served as controls to assess drug effects on normal cells. Rivaroxaban concentrations ranged from 0.1 to 1000 µg/ml. The selective toxicity index was computed to determine tumor-specific cytotoxicity. Additionally, molecular docking simulations were conducted to assess rivaroxaban's binding affinity to TRAP1, Bcl-2/Bcl-xL, and BAK-BAX proteins.Results: The study findings showed a dual effect of rivaroxaban on cervical cancer growth. It selectively inhibited cancer cell growth at concentrations of 10 and 100 µg/ml. However, increased cancer proliferation was observed at a concentration of 1000 µg/ml. The IC50 values were 319.45 and 86.2 µg/ml at 24 and 72 hours, respectively. Molecular docking results indicated that rivaroxaban has affinity for binding with TRAP1, Bcl-2/Bcl-xl, and BAX-BAK proteins, with docking scores of -8.1, -8.2, and -10.7 kcal/mol, respectively. These findings may shed light on the potential anticancer and carcinogenic effects of rivaroxaban. Conclusion: Based on our findings and the pharmacological profile of rivaroxaban, its potential carcinogenicity appears minimal since it has not been administered at doses exceeding therapeutic levels due to its anticoagulant effects. Additionally, low-dose rivaroxaban may be the optimal anticoagulant for cancer patients, especially those with cervical cancer, considering its potential anticancer properties.