Carotenoid 9', 10'‐monooxygenase: Tumor Suppressor Activity in Prostate Cancer

Abstract

Carotenoid cleavage monooxygenases (CMOs) are a class of enzymes that cleave various carotenoids (including carotenes, lycopene) to apocarotenoids and retinoids. Carotenoid 9’,10’‐monooxygenase (CMO2) regulates lycopene metabolism. Since lycopene intake may have preventive and therapeutic effects in prostate cancer, we investigated CMO2 in human normal prostate, cancer tissue and prostate cancer cell lines. CMO2 expression is significantly higher in human normal prostate tissues than that in prostate cancers. In prostate cancer cell lines, CMO2 expression is higher in androgen‐sensitive than in androgen‐resistant cells. Lycopene treatment significantly increases CMO2 expression and reduces cell proliferation in androgen‐sensitive cells, but does not affect CMO2 expression or cell growth in androgen‐resistant cells. Over‐expression of CMO2 in various prostate cancer cell lines decreased proliferation regardless of lycopene co‐treatment or androgen‐responsiveness. Exogenous CMO2 expression reduced NF‐κB activity by interfering with phosphorylation and DNA binding of the p65 and p50 components of the NF‐κB complex. CMO2 over‐expression also increased PPAR and p38 activity and reduced Akt1, ERK2 and JNK2 activity. CMO2 suppression apparently contributes to development of human prostate cancer. We also describe previously unexpected functions for the enzyme CMO2, apparently independent of a role in carotenoid metabolism. Our findings (1) suggest that CMO2 may be a tumor suppressor in prostate cancer and (2) support a role of lycopene in the prevention or treatment of androgen‐sensitive prostate cancer (NIH HD42174, RR18728).