Abstract
The novel atypical retinoid E-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926, 4) exhibited a potent antiproliferative activity on a large panel of human tumor cells. Despite almost complete loss of ability to activate RARs, the compound was an effective apoptosis inducer and surprisingly produced DNA damage, that likely contributes to the proapoptotic activity. Following oral administration, 4 was well tolerated and caused tumor growth inhibition in the ovarian carcinoma, A2780/DX, and in the human melanoma, MeWo, growing in nude mice, thus supporting the therapeutic interest of the novel agent.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adamantane / analogs & derivatives
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Adamantane / chemical synthesis*
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Adamantane / chemistry
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Adamantane / pharmacology
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Apoptosis*
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Cinnamates / chemical synthesis*
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Cinnamates / chemistry
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Cinnamates / pharmacology
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DNA Damage
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Drug Screening Assays, Antitumor
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Female
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Humans
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Melanoma / drug therapy
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Melanoma / pathology
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Mice
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Mice, Nude
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / pathology
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Protein Isoforms
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism
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Retinoids / chemical synthesis*
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Retinoids / chemistry
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Retinoids / pharmacology
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Structure-Activity Relationship
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Transfection
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Transplantation, Heterologous
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Tumor Cells, Cultured
Substances
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3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid
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Antineoplastic Agents
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Cinnamates
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Protein Isoforms
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Receptors, Retinoic Acid
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Retinoids
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Adamantane