Beta-carotene inhibits growth of human colon carcinoma cells in vitro by induction of apoptosis.
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.
Briviba
K
K
Institute of Nutritional Physiology, Federal Research Centre for Nutrition, Karlsruhe, Germany.
Schnäbele
K
K
Schwertle
E
E
Blockhaus
M
M
Rechkemmer
G
G
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D005562:Formazans / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D013778:Tetrazolium Salts / Q000494:pharmacology; D014801:Vitamin A / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism / Q000494:pharmacology*
C110656:2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; D005562:Formazans; D006131:Growth Inhibitors; D013778:Tetrazolium Salts; D019207:beta Carotene; D014801:Vitamin A; C079782:MTT formazan; D020928:Mitogen-Activated Protein Kinases