Lycopene and other carotenoids inhibit estrogenic activity of 17β-estradiol and genistein in cancer cells

Abstract

Epidemiological evidence suggests that carotenoids prevent several types of cancer, including mammary and endometrial cancers. On the other hand, such studies have also shown that estrogens are the most important risk factors for these cancer types. Genistein, the phytoestrogen mainly found in soy, also shows significant estrogenic activity when tested at concentrations found in human blood. The aim of this study was to determine whether carotenoids inhibit signaling of steroidal estrogen and phytoestrogen which could explain their cancer preventive activity. Similar to the known effect of 17beta-estradiol (E(2)), treatment of breast (T47D and MCF-7) and endometrial (ECC-1) cancer cells with phytoestrogens induced cell proliferation, cell-cycle progression and transactivation of the estrogen response element (ERE). However, each of the tested carotenoids (lycopene, phytoene, phytofluene, and beta-carotene) inhibited cancer cell proliferation induced by either E(2) or genistein. The inhibition of cell growth by lycopene was accompanied by slow down of cell-cycle progression from G1 to S phase. Moreover, the carotenoids inhibited estrogen-induced transactivation of ERE that was mediated by both estrogen receptors (ERs) ERalpha and ERbeta. The possibility that this inhibition results from competition of carotenoid-activated transcription systems on a limited pool of shared coactivators with the ERE transcription system was tested. Although cotransfection of breast and endometrial cancer cells with four different coactivators (SRC-1, SRC-2, SRC-3, and DRIP) strongly stimulated ERE reporter gene activity, it did not oppose the inhibitory effect of carotenoids. These results suggest that dietary carotenoids inhibit estrogen signaling of both 17beta-estradiol and genistein, and attenuate their deleterious effect in hormone-dependent malignancies.

A comprehensive review on the colorless carotenoids phytoene and phytofluene

“…The effect of phytoene, phytofluene and other carotenoids in the inhibition of cell proliferation and estrogen transcriptional activity induced by estrogens (17b-estradiol and soy phytoestrogens) was studied by Hirsch et al [140]. To this end, cell lines of breast (MCF-7 and T47D) and endometrial (ECC-1) hormone-dependent cancer cells were treated with increasing amounts of either 17b-estradiol or the soy phytoestrogen genistein in presence or absence of the carotenoids.…”

“…Both phytoene and phytofluene at a concentration of 4-6 lM in the medium were shown to inhibit the proliferation of the cells induced by the tested estrogens. Additionally, all the carotenoids evaluated inhibited the estrogen-induced transactivation of the estrogen response element (ERE) [140].…”

Paprika and/or marigold extracts in diets for laying hens

“…The quality of the shell is affected by several factors, such as illness, nutritional status of the flock, heat stress, and bird age (ROBERTS, 2004). According to reports, lutein and zeaxanthin, carotenoids present in marigold extract, inhibit the estrogenic activity in several tissues (HIRSCH et al, 2007;ZHANG et al, 2012); this is probably the reason for the lower percentage and thickness of the eggshell. The shell consists mainly of calcium carbonate (CaCO 3 ).…”

Modulation of gene methylation by genistein or lycopene in breast cancer cells

“…There is a very wide range of mean plasma lycopene levels, 0.07-1.79 lM [Mayne et al, 1999]. Lycopene consumption has been closely linked with the chemoprevention of a number of cancers, particularly prostate cancer [Ellinger et al, 2006]; and evidence for its utility in the breast cancer arena is emerging [Karas et al, 2000;Hirsch et al, 2007;Thomson et al, 2007]. Yet discrepancies remain in the literature pertaining the effectiveness of lycopene as a chemopreventive agent [Kavanaugh et al, 2007].…”