Journal Article

Inhibition of chemically-induced neoplastic transformation by a novel tetrasodium diphosphate astaxanthin derivative

Laura M. Hix, Dean A. Frey, Mark D. McLaws, Marianne Østerlie, Samuel F. Lockwood and John S. Bertram

in Carcinogenesis

Volume 26, issue 9, pages 1634-1641
Published in print September 2005 | ISSN: 0143-3334
Published online May 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi121
Inhibition of chemically-induced neoplastic transformation by a novel tetrasodium diphosphate astaxanthin derivative

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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 ∼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.

Keywords: AST, astaxanthin; CTX, canthaxanthin; Cx32, connexin 32; Cx43, connexin 43; dAST, disodium salt disuccinate ester of astaxanthin; GJIC, gap junctional intercellular communication; MCA, methylcholanthrene; pAST, tetrasodium diphosphate astaxanthin; THF, tetrahydrofuran; TTNPB, 5,6,7,8-tetrahydro-(5,5,8,8-tetramethyl-2-napthyl) propenyl benzoic acid.

Journal Article.  7330 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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