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.