Screening of the antiproliferative activity of lycopene isomers in a panel of human cancer cell lines: Lycopene Z-isomers exhibit greater activity than the all-E-isomer

Abstract Lycopene occurs as multiple geometrical isomers, whereas most studies on its cancer-related effects have focused on the all- E -isomer or on preparations with an undefined isomer composition. In this study, the antiproliferative activities of all- E -isomer-rich lycopene preparation ( E -LYC) and Z -isomer-rich lycopene preparation ( Z -LYC) were compared using a panel of 102 human cancer cell lines under identical experimental conditions. Z -LYC showed a broader antiproliferative profile than E -LYC, with IC 50 values within the tested concentration range (3.16–31,600 nM) in 91 and 16 cell lines, respectively. Tissue sensitivity analysis indicated that lymphoid malignancies and leukemia were relatively sensitive to Z -LYC, with additional sensitivity observed in bone, soft tissue, ovarian, and testicular germ cell tumors. Phenotypic similarity analysis further showed broader correlations for Z -LYC than E -LYC with reference anticancer agents, suggesting a more distinct biological response profile at the cellular level. Preliminary molecular docking simulations also suggested that lycopene Z -isomers may interact more favorably than the all- E -isomer with selected cancer-related proteins. These findings indicate that lycopene Z -isomers exhibit broader antiproliferative activity than the all- E -isomer in this in vitro screening platform and warrant further mechanistic and in vivo studies.