Effect of naringenin and its combination with cisplatin in cell death, proliferation and invasion of cervical cancer spheroids
Oswaldo Pablo Martínez‐Rodríguez, Alejandro González-Torres, Luis Marat Álvarez-Salas, Humberto Hernández‐Sánchez, Blanca Estela García‐Pérez, María del Rocío Thompson-Bonilla, María Eugenia Jaramillo‐Flores
Abstract
the loss of cell membrane integrity. Furthermore, it did not activate caspases 3, 7, 8, and 9, suggesting that the cytotoxic effect was by necrotic cell death instead of apoptosis. Additionally, proliferation in the G0/G1 phase of the cell cycle was inhibited. Cell invasion also decreased as time progressed. Later, we determined if naringenin could improve the anti-tumor effect of cisplatin. The combination of naringenin with low concentrations of cisplatin improved the effect of the drug by significantly decreasing cell viability, potentiating the induction of cytotoxicity and decreasing the invasive capacity of the spheroids. Since these effects are regulated by some key proteins, molecular docking results indicated the interaction of naringenin with RIP3 and MLKL, cyclin B and with matrix metalloproteases 2 and 9. The results showed the anti-tumor effect of naringenin on the HeLa spheroids and improved effect of the cisplatin at low concentrations in combination with naringenin, placing flavonoids as a potential adjuvant in the therapy against cervical cancer.