Inhibition of Mammary Carcinoma Growth by Retinoidal Benzoic Acid Derivatives

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Abstract
The growth of many breast carcinoma cell lines is inhibited by vitamin A, and derivatives as well as synthetic retinoids. New retinoidal derivatives have recently been synthesized. These retinoidal benzoic acid derivatives displayed enhanced potency in their ability to reverse hamster tracheal keratinization and inhibit ornithine decarboxylase induction in mouse epidermis. We therefore screened a series of analogues of these compounds for their ability to inhibit human breast carcinoma cell proliferation utilizing three estrogen receptor-positive and two estrogen receptor-negative cell lines. The compound (E)-4–2-(5,6,7,8)tetrahydro-5,5,8,8-tetramethyl-2-naphtalenyl)propenyl benzoic acid (Ro 1374–10) was approximately 2–3 orders of magnitude more potent than all-trans-retinoic acid in inhibiting breast carcinoma cell proliferation while the compound SRI-6409–40, which differs from Ro 1374–10 only by the position of a methyl group, was 50-fold more potent than Ro 1374–10. All of the compounds tested displayed were inactive against the estrogen receptor-negative breast carcinoma lines.

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