Carotenoids have been implicated in numerous epidemiological studies as being protective against
cancer at many sites, and their chemopreventive properties have been confirmed in laboratory studies.
Astaxanthin (AST), primarily a
carotenoid of marine origin, responsible for the pink coloration of salmon, shrimp and lobster, has received relatively little attention. As with other
carotenoids, its highly lipophilic properties complicate delivery to model systems. To overcome this issue we have synthesized a novel
tetrasodium diphosphate astaxanthin (pAST) derivative with aqueous dispersibility of 25.21 mg/ml. pAST was delivered to C3H/10T1/2 cells in an aqueous/
ethanol solution and compared with non-esterified AST dissolved in
tetrahydrofuran. We show pAST to (i) upregulate
connexin 43 (
Cx43)
protein expression; (ii) increase the formation of
Cx43 immunoreactive plaques; (iii) upregulate gap junctional intercellular communication (GJIC); and (iv) cause 100% inhibition of
methylcholanthrene-induced neoplastic transformation
at 10(-6) M. In all these assays, pAST was superior to non-esterified AST itself; in fact, pAST exceeded the potency of all other previously tested
carotenoids in this model system. Cleavage of pAST to non-esterified (free) AST and uptake into cells was also verified by HPLC; however, levels of free AST were approximately 100-fold lower than in cells treated with AST itself, suggesting that pAST possesses intrinsic activity. The dual properties of water dispersibility (enabling parenteral administration in vivo) and increased potency should prove extremely useful in the future development of
cancer chemopreventive agents.