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

We have studied the effects of ß-carotene(ß03-C),a vitamin A precursor of plant origin, and canthaxanthin (CTX),a non-provitamin A carotenoid, on the neoplastic transformationof C3H/10T1/2 murine fibroblast cells. Chemical transformationin this well-characterized cell system has previously been shownto be reversibly inhibited by retinoids, compounds with vitaminA-like activity. Here we show that both ß-C and CTXinhibit 3-methycholanthrene (MCA)-induced transformation withED⁵⁰S of 9 x10-⁷M and 2x10-⁷ M, respectively. Both carotenoidsfailed to inhibit X-ray-induced transformation when the cellswere treated prior to and during irradiation. However, whenthe drugs were added 1 week after X-irradiation and maintainedin the medium thereafter, as in the chemical transformationprotocol, both carotenoids inhibited subsequent developmentof transformed foci in a dose-dependent manner. Again, CTX wasmore effective than ß3-C, such that 3 x 10-⁶M completelyinhibited radio-genicaly-induced foci. Similar to the previouslydescribed action of retinoids, the inhibition of MCA-inducedtransformation was reversible; developed upon removal of thedrug, transformed foci developed within 2 weeks, indicatingthat the carotenoids were not specifically toxic to initiatedcells. Although both carotenoids caused a small dose-dependentdecrease in the growth rate of both parental and initiated 10T1/2cells, they did not markedly affect colony size or number whenthe cells were treated as in the transformation assays, nordid they influence the expression of neoplasia of two transformedcell lines. Although the actions of ß3-C and CTX aresimilar to those of retinoids in the 10T1/2 system, we suggestthat the carotenoids act via a different mechanism, since CTXcannot be converted to active retinoids in mammalian cells,and there is no evidence that 10T1/2 cells can convert ß-Cto vitamin A. We suggest that the carotenoids, lipid anti-oxidantproperties may be responsible for their inhibitory actions ontransformation.