Lycopene mitigates DHT-induced apoptosis and oxidative stress in human granulosa cell line KGN by regulating the Nrf2 pathway

Recently, accumulating evidence has proved that apoptosis and oxidative stress exert essential roles in the development of polycystic ovarian syndrome (PCOS). Besides, multiple natural products have been identified to be related to the PCOS process.

This investigation aimed to elucidate the effects and mechanisms of lycopene on granulosa-like tumor cell line (KGN) in the presence of dihydrotestosterone (DHT). KGN cells were treated using DHT or lycopene and cell survival rate was tested by cell counting kit 8 (CCK-8) assay. Also, flow cytometry, western blot as well as enzyme-linked immunosorbent assay (ELISA) were utilized to detect cell apoptosis, protein level and the marker of oxidative stress. ROS accumulation was observed with DCFH-DA dye. The nuclear factor-erythroid 2-related factor (Nrf2) expression in KGN cells was reduced via small interfering RNA (siRNA). The nuclear translocation of Nrf2 was determined through immunofluorescence (IF) analysis.

Lycopene effectively reversed DHT-induced apoptosis in addition to oxidative stress in KGN cells. Besides, lycopene treatment obviously activated Nrf2 signaling and accelerated nuclear translocation of Nrf2 in KGN cells. Nrf2 depletion partially counteracted the role of lycopene in DHT-mediated apoptosis as well as oxidative stress in KGN cells.

In summary, this work revealed that lycopene alleviates oxidative stress and apoptosis in KGN cells in the presence of DHT, which at least partly by depending on the activation of Nrf2 cascade signal at the molecular level.