Antitumor activity of the retinoid-related molecules (E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926) and 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) in F9 teratocarcinoma: Role of retinoic acid receptor gamma and retinoid-independent pathways
| Autor: | Lucio Merlini, Mineko Terao, Maddalena Fratelli, Maurizio Gianni, Ivan Raska, Luisa Diomede, Enrico Garattini, Paolo Carminati, Edoardo Parrella, Cécile Rochette-Egly, Mami Kurosaki, Michele Tavecchio, Sabrina Dallavalle, Claudio Pisano, Maria Monica Barzago |
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| Přispěvatelé: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Teratocarcinoma
MESH: Cell Death Receptors Retinoic Acid Cellular differentiation Messenger Retinoic Acid Adamantane Mice SCID Mice 0302 clinical medicine Cytosol retinoids teratocarcinoma ST1926 MESH: Cytosol Chlorocebus aethiops Receptors MESH: Animals Retinoid MESH: Mice SCID Receptor Cells Cultured 0303 health sciences Cultured Cell Death Cell Differentiation MESH: Adamantane MESH: Gene Expression Regulation Neoplastic Gene Expression Regulation Neoplastic MESH: COS Cells Biochemistry 030220 oncology & carcinogenesis MESH: Calcium COS Cells Molecular Medicine medicine.drug MESH: Cells Cultured G2 Phase MESH: Cell Differentiation medicine.drug_class Cells MESH: Teratocarcinoma Mitosis Antineoplastic Agents Tretinoin Biology SCID Cercopithecus aethiops 03 medical and health sciences Retinoids MESH: Gene Expression Profiling In vivo medicine Animals Humans MESH: Retinoids RNA Messenger Calcium Cinnamates Disease Models Animal Gene Expression Profiling Pharmacology MESH: Mice 030304 developmental biology MESH: RNA Messenger MESH: Receptors Retinoic Acid Neoplastic MESH: Humans MESH: Tretinoin Animal [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Settore CHIM/06 - Chimica Organica Retinoic acid receptor gamma MESH: Mitosis Molecular biology MESH: Cercopithecus aethiops In vitro Retinoic acid receptor MESH: G2 Phase MESH: Cinnamates Gene Expression Regulation Disease Models RNA MESH: Antineoplastic Agents MESH: Disease Models Animal |
| Zdroj: | Molecular Pharmacology Molecular Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 2006, 70 (3), pp.909-24. ⟨10.1124/mol.106.023614⟩ |
| ISSN: | 0026-895X |
| Popis: | International audience; The retinoid-related molecules (RRMs) ST1926 [(E)-3-(4'-hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid] and CD437 (6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid) are promising anticancer agents. We compared the retinoic acid receptor (RAR) trans-activating properties of the two RRMs and all-trans-retinoic acid (ATRA). ST1926 and CD437 are better RARgamma agonists than ATRA. We used three teratocarcinoma cell lines to evaluate the significance of RARgamma in the activity of RRMs: F9-wild type (WT); F9gamma-/-, lacking the RARgamma gene; F9gamma51, aF9gamma-/-derivative, complemented for the RARgamma deficit. Similar to ATRA, ST1926 and CD437 activate cytodifferentiation only in F9-WT cells. Unlike ATRA, ST1926 and CD437 arrest cells in the G2/M phase of the cell cycle and induce apoptosis in all F9 cell lines. Our data indicate that RARgamma and the classic retinoid pathway are not relevant for the antiproliferative and apoptotic activities of RRMs in vitro. Increases in cytosolic calcium are fundamental for apoptosis, in that intracellular calcium chelators abrogate the process. Comparison of the gene expression profiles associated with ST1926 and ATRA in F9-WT and F9gamma-/-indicates that the RRM activates a conspicuous nonretinoid response in addition to the classic and RAR-dependent pathway. The pattern of genes regulated by ST1926 selectively, in a RARgamma-independent manner, provides novel insights into the possible molecular determinants underlying the activity of RRMs in vitro. Furthermore, it suggests that RARgamma-dependent responses are relevant to the activity of RRMs in vivo. Indeed, the receptor hinders the antitumor activity in vivo, in that both syngeneic and immunosuppressed SCID mice bearing F9gamma-/- tumors have increased life spans after treatment with ST1926 and CD437 relative to their F9-WT counterparts. |
| Databáze: | OpenAIRE |
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