β-Carotene and canthaxanthin inhibit chemically- and physically- induced neoplastic transformation in 10T1/2 cells

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Abstract
We have studied the effects of β-carotene(β03-C), a vitamin A precursor of plant origin, and canthaxanthin (CTX), a non-provitamin A carotenoid, on the neoplastic transformation of C3H/10T1/2 murine fibroblast cells. Chemical transformation in this well-characterized cell system has previously been shown to be reversibly inhibited by retinoids, compounds with vitamin A-like activity. Here we show that both β-C and CTX inhibit 3-methycholanthrene (MCA)-induced transformation with ED 50 S of 9 ×10- 7 M and 2×10- 7 M, respectively. Both carotenoids failed to inhibit X-ray-induced transformation when the cells were treated prior to and during irradiation. However, when the drugs were added 1 week after X-irradiation and maintained in the medium thereafter, as in the chemical transformation protocol, both carotenoids inhibited subsequent development of transformed foci in a dose-dependent manner. Again, CTX was more effective than β3-C, such that 3 × 10- 6 M completely inhibited radio-genicaly-induced foci. Similar to the previously described action of retinoids, the inhibition of MCA-induced transformation was reversible; developed upon removal of the drug, transformed foci developed within 2 weeks, indicating that the carotenoids were not specifically toxic to initiated cells. Although both carotenoids caused a small dose-dependent decrease in the growth rate of both parental and initiated 10T1/2 cells, they did not markedly affect colony size or number when the cells were treated as in the transformation assays, nor did they influence the expression of neoplasia of two transformed cell lines. Although the actions of β3-C and CTX are similar to those of retinoids in the 10T1/2 system, we suggest that the carotenoids act via a different mechanism, since CTX cannot be converted to active retinoids in mammalian cells, and there is no evidence that 10T1/2 cells can convert β-C to vitamin A. We suggest that the carotenoids, lipid anti-oxidant properties may be responsible for their inhibitory actions on transformation.

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