β-Carotene Inhibits Growth of Human Colon Carcinoma Cells in Vitro by Induction of Apoptosis

Abstract

Epidemiological studies suggest that beta-carotene is able to modulate the risk of cancer. A number of in vitro studies reported that beta-carotene inhibits the growth of cancer cells; however, so far little is known about the molecular mechanisms of the antiproliferative effect of beta-carotene. Here we have investigated the effects of two beta-carotene preparations, (i) beta-carotene dissolved in tetrahydrofuran (final concentration in cell culture medium: 0.5%) and (ii) beta-carotene incorporated in a water dispersible bead form, on cultured human colon carcinoma cells HT29. The treatment of cells with beta-carotene up to 30 microM for 72 h led to a significant increase in the cellular beta-carotene concentration and formation of retinol. Beta-Carotene showed only low cytotoxicity for confluent cells tested up to 30 microM, but at dietary relevant concentrations for the intestinal tract (10, 30 microM) beta-carotene was strongly cytotoxic for growing cells and induced apoptosis in HT29 cells as assessed by the Annexin-V assay (the maximal effect was observed 15 h after treatment with beta-carotene). Exposure of cells to retinol at concentrations yielding cellular retinol levels similar to those observed by beta-carotene treatment had no antiproliferative or cytotoxic effect. Furthermore, beta-carotene did not affect the activation of the extracellular signal-regulated kinases (ERK1 and ERK2) that are essential for cellular growth. In summary, beta-carotene can inhibit growth of human colon carcinoma cells in vitro by induction of apoptosis in proliferating cells.

β-Carotene-induced apoptosis is mediated with loss of Ku proteins in gastric cancer AGS cells

“…For instance, human colon carcinoma cells were cultured in the media containing bcarotene (30 lM). After 3 days, intracellular levels of bcarotene and retinol were 22 pmol/10 6 cells and 45 pmol/ 10 6 cells, respectively (Briviba et al 2001). Even though cellular uptake of b-carotene may be dependent on cell types and culture time, we could presume that b-carotene (100 lM) treatment to the medium may increase intracellular levels of b-carotene (about 70 pmol/10 6 cells) and retinol (about 150 pmol/10 6 cells), based on the previous study (Briviba et al 2001).…”

“…After 3 days, intracellular levels of bcarotene and retinol were 22 pmol/10 6 cells and 45 pmol/ 10 6 cells, respectively (Briviba et al 2001). Even though cellular uptake of b-carotene may be dependent on cell types and culture time, we could presume that b-carotene (100 lM) treatment to the medium may increase intracellular levels of b-carotene (about 70 pmol/10 6 cells) and retinol (about 150 pmol/10 6 cells), based on the previous study (Briviba et al 2001). Further study should be performed to determine the intracellular levels of b-carotene and retinol after treatment of b-carotene in various types of cells and different culture conditions.…”

“…Treatment of b-carotene in the media increased intracellular concentrations of b-carotene in a concentration-dependent manner (Eicker et al 2003;Rodríguez et al Briviba et al 2001). For instance, human colon carcinoma cells were cultured in the media containing bcarotene (30 lM).…”

Possible Effects of Lycopene and Silymarin on Rat Liver Functions and Oxidative Stress Markers

“…Epidemiological studies have indicated that food products which contain lycopene, the most potent antioxidant compound among carotenoids, have chemopreventive effects against cancers and other diseases [2]. Human cell studies showed that lycopene can reduce oxidative DNA damage, stimulate the immune system and facilitate intercellular communication [3]. Many reports on the health benefits of lycopene are attributed to its ability to protect cells against oxidative damage [2][3][4][5][6].…”

“…Human cell studies showed that lycopene can reduce oxidative DNA damage, stimulate the immune system and facilitate intercellular communication [3]. Many reports on the health benefits of lycopene are attributed to its ability to protect cells against oxidative damage [2][3][4][5][6]. Besides, it has also been observed that silymarin possesses antioxidant, antiinflammatory, antifibrotic and antiproliferative properties.…”