Lycopene inhibits proliferation, induces apoptosis, and suppresses migration in cervical cancer cells: involvement of PI3K/Akt signaling.

Cervical cancer remains a major cause of mortality worldwide, highlighting the need for alternative therapeutic strategies. Lycopene, a dietary carotenoid with known antioxidant properties, has demonstrated anticancer activity in several malignancies; however, its mechanistic effects in cervical cancer remain poorly understood. We hypothesize that lycopene inhibits the growth of cervical cancer cell lines and certain cancer-related processes. Therefore, we performed an in vitro study to investigate lycopene's effects on proliferation, viability, migration, and apoptosis in three cervical cancer cell lines (HeLa, SiHa, and ViBo) using lycopene concentrations ranging from 1.25 to 40 µM, and further evaluated the underlying mechanisms using 2.5 and 40 µM lycopene, and evaluated its effects on non-malignant cardiomyoblasts (H9c2). Lycopene significantly reduced proliferation and cell viability and impaired migration in all cancer cell lines. Flow cytometry revealed increased apoptosis, associated with time-dependent modulation of the Bax/Bcl-2 ratio and caspase-3 activation. Mechanistically, lycopene decreased Akt phosphorylation without affecting total Akt or PI3K levels, indicating the participation of the PI3K/Akt survival pathway. Importantly, pharmacological PI3K inhibition with wortmannin supported this pathway's involvement in mediating lycopene-induced effects. Notably, lycopene at lower concentrations showed minimal cytotoxicity in H9c2 cells, suggesting some selectivity toward cancer cells. Together, these findings show that lycopene decreases proliferation and viability, promotes apoptosis, and suppresses migration in cervical cancer cells; these effects were associated with PI3K/Akt signaling, indicating that this pathway may contribute to its anticancer effects and highlighting lycopene's potential as a therapeutic candidate.