Lycopene is a more potent inhibitor of human cancer cell proliferation than either α‐carotene or β‐carotene

Abstract

The antiproliferative properties of lycopene, the major tomato carotenoid, were compared with those of alpha- and beta-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 1-2 microM; alpha- and beta-carotene were far less effective inhibitors. For example, in Ishikawa cells, a 4-fold higher concentration of alpha-carotene or a 10-fold higher concentration of beta-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 autocrine/paracrine regulators of mammary and endometrial cancer cell growth. Therefore, lycopene interference in this major autocrine/paracrine system may open new avenues for research on the role of lycopene in the regulation of endometrial cancer and other tumors.

Effect of lycopene supplementation on insulin-like growth factor-1 and insulin-like growth factor binding protein-3: a double-blind, placebo-controlled trial

“…A number of studies have suggested that lycopene's effect on chronic disease may be mediated through effects on IGF-1. One study (Levy et al, 1995) compared the effect of lycopene on cancer cell proliferation with a-carotene or b-carotene. Lycopene was much more effective than the other two compounds in inhibiting human breast, endometrial and lung cancer IGF-1-stimulated cell growth.…”

“…A recent systematic review showed circulating IGF-1 to be associated with increased risk of prostate and pre-menopausal breast cancer (Renehan et al, 2004). A number of studies have suggested a link between lycopene and IGF-1-stimulated cell proliferation in vitro (Levy et al, 1995;Karas et al, 2000), and an inverse association has been demonstrated between cooked tomato consumption and circulating IGF-1 concentrations in vivo (Mucci et al, 2001;Gunnell et al, 2003). Other studies have, however, failed to show an association between circulating IGF-1 and lycopene concentrations (Graydon et al, 2003;Vrieling et al, 2004).…”

Dietary Determinants of Circulating Insulin-like Growth Factor (IGF)-I and IGF Binding Proteins 1, -2 and -3 in Women in the Netherlands

“…In three of these studies, higher intake of cooked or processed tomatoes or lycopene was associated with either lower IGF-I levels [14], higher IGFBP-3 levels [22], or a lower IGF-I/IGFBP-3 molar ratio [18]. Two in vitro studies have shown that lycopene can inhibit IGF-I-stimulated growth of endometrium and mammary cancer cell lines [34,35]. In these studies, lycopene reduced IGF-I receptor signaling, and increased levels of membrane-associated IGFBPs [35].…”

“…Additionally, results differed for pre-and postmenopausal women [31], which suggests that the effects of phytoestrogens on the IGF system components may be dependent on endogenous estradiol concentrations. Lycopene is an anti-oxidant mainly found in cooked or processed tomatoes, and has been suggested to interfere with IGF signaling in experimental studies [34][35][36]. Also in cross-sectional studies lycopene [22] or cooked or processed tomatoes [14,18] were associated with IGF-I or IGFBP-3.…”

Lycopene and prostate cancer

“…53 These include an upregulation in intercellular gap junctions, 54 an increase in cellular differentiation 55 and alterations in phosphorylation of some regulatory proteins. 56 Little is known regarding the role or indeed importance of these effects in vivo, however, lycopene has been demonstrated to be significantly more efficient than any carotene in inhibiting insulin-like growth factor type 1 (IGF1) induced proliferation of a number of tumour cell lines 57 and decrease the occurrence of both spontaneous and chemically induced mammary tumours in animal models. 58,59 In prostate cancer, in particular, a study has demonstrated inhibition of cell line proliferation in the presence of physiological concentrations of lycopene in combination with alpha-tocopherol.…”