AbstractThe antiproliferative properties of lycopene, the major tomato carotenoid, were compared with those ofα‐andβ‐carotene. Lycopene, delivered in cell culture medium from stock solutions in tetrahydrofuran, strongly inhibited proliferation of endometrial (Ishikawa), mammary (MCF‐7), and lung (NCI‐H226) human cancer cells with half‐maximal inhibitory concentration of 1–2μ?;α‐andβ‐carotene were far less effective inhibitors. For example, in Ishikawa cells, a 4‐fold higher concentration ofα‐carotene or a 10‐fold higher concentration ofβ‐carotene was needed for the same order of growth suppression. The inhibitory effect of lycopene was detected after 24 hours of incubation, and it was maintained for at least three days. In contrast to cancer cells, human fibroblasts were less sensitive to lycopene, and the cells gradually escaped growth inhibition over time. In addition to its inhibitory effect on basal endometrial cancer cell proliferation, lycopene also suppressed insulin‐like growth factor‐I‐stimulated growth. Insulin‐like growth factors are major autocrinelparacrine regulators of mammary and endometrial cancer cell growth. Therefore, lycopene interference in this major autocrinelparacrine system may open new avenues for research on the role of lycopene in the regulation of endometrial cancer and other tumors.