Cited by 651Natural product bioactivities and synthesisPhytochemical Studies and BioactivitiesPharmacological Effects of Natural Compounds

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Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer

Liby, Karen T., Yore, Mark M., Sporn, Michael B.·2007·Nature Reviews Cancer

DOI 10.1038/nrc2129

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Abstract

Synthetic oleanane triterpenoids and rexinoids are two new classes of multifunctional drugs. They are neither conventional cytotoxic agents, nor are they monofunctional drugs that uniquely target single steps in signal transduction pathways. Synthetic oleanane triterpenoids have profound effects on inflammation and the redox state of cells and tissues, as well as being potent anti-proliferative and pro-apoptotic agents. Rexinoids are ligands for the nuclear receptor transcription factors known as retinoid X receptors. Both classes of agents can prevent and treat cancer in experimental animals. These drugs have unique molecular and cellular mechanisms of action and might prove to be synergistic with standard anti-cancer treatments.

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A novel dicyanotriterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile, active at picomolar concentrations for inhibition of nitric oxide production
Honda, T., Honda, Y., Favaloro, F. G., Gribble, G. W., Suh, N., Place, A. E., Rendi, M. H., & Sporn, M. B. (2002) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(02)00105-1 · Cited by 143
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Suppression of mammary tumorigenesis in transgenic mice by the RXR-selective retinoid, LGD1069.
Wu, K., Kim, H.-T., Rodriquez, J. L., Hilsenbeck, S. G., Mohsin, S. K., Xu, X., Lamph, W. W., Kuhn, J. G., Green, J. E., & Brown, P. H. (2002) · PubMed · Cited by 143
Bexarotene: a clinical review
Farol, L., & Hymes, K. B. (2004) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.4.2.180 · Cited by 141
The Synthetic Triterpenoids CDDO-Methyl Ester and CDDO-Ethyl Amide Prevent Lung Cancer Induced by Vinyl Carbamate in A/J Mice
Liby, K. T., Royce, D. B., Williams, C. R., Risingsong, R., Yore, M. M., Honda, T., Gribble, G. W., Dmitrovsky, E., Sporn, T. A., & Sporn, M. B. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4534 · Cited by 141
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The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism
Ito, Y., Pandey, P., Sporn, M. B., Datta, R., Kharbanda, S., & Kufe, D. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.5.1094 · Cited by 138
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The Synthetic Triterpenoid 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic Acid Induces Caspase-Dependent and -Independent Apoptosis in Acute Myelogenous Leukemia
Konopleva, M. Y., Tsao, T., Estrov, Z. E., Lee, R.-M., Wang, R., Jackson, C. E., McQueen, T. J., Monaco, G., Munsell, M. F., Belmont, J. W., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2402 · Cited by 136
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The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti–multiple myeloma (MM) activity and overcome bortezomib resistance
Chauhan, D., Li, G., Podar, K., Hideshima, T., Shringarpure, R., Catley, L. P., Mitsiades, C. S., Munshi, N. C., Tai, Y., Suh, N., et al. (2003) · Blood · doi:10.1182/blood-2003-08-2873 · Cited by 131
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Synthetic Triterpenoids Cooperate with Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand to Induce Apoptosis of Breast Cancer Cells
Hyer, M. L., Croxton, R., Krajewska, M., Krajewski, S., Kress, C. L., Lü, M., Suh, N., Sporn, M. B., Cryns, V. L., Zapata, J. M., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3319 · Cited by 128
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The novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid induces apoptosis of human myeloid leukemia cells by a caspase-8-dependent mechanism.
Ito, Y., Pandey, P., Place, A., Sporn, M. B., Gribble, G. W., Honda, T., Kharbanda, S. M., & Kufe, D. W. (2000) · PubMed · Cited by 126
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Multi-Institutional Phase I/II Trial of Oral Bexarotene in Combination With Cisplatin and Vinorelbine in Previously Untreated Patients With Advanced Non–Small-Cell Lung Cancer
Khuri, F. R., Rigas, J. R., Figlin, R. A., Gralla, R. J., Shin, D. M., Munden, R. F., Fox, N., Huyghe, M. R., Kean, Y., Reich, S. D., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.10.2626 · Cited by 121
Rexinoid-Triggered Differentiation and Tumor-Selective Apoptosis of Acute Myeloid Leukemia by Protein Kinase A–Mediated Desubordination of Retinoid X Receptor
Altucci, L., Rossin, A., Hirsch, O., Nebbioso, A., Vitoux, D., Wilhelm, E., Guidez, F., Simone, M. D., Schiavone, E. M., Grimwade, D. J., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3569 · Cited by 120
Olive Fruit Extracts Inhibit Proliferation and Induce Apoptosis in HT-29 Human Colon Cancer Cells
Juan, M. E., Wenzel, U., Ruíz-Gutiérrez, V., Daniel, H., & Planas, J. M. (2006) · Journal of Nutrition · doi:10.1093/jn/136.10.2553 · Cited by 119
Novel Synthetic Oleanane and Ursane Triterpenoids with Various Enone Functionalities in Ring A as Inhibitors of Nitric Oxide Production in Mouse Macrophages
Honda, T., Gribble, G. W., Suh, N., Finlay, H. J., Rounds, B. V., Bore, L., Favaloro, F. G., Wang, Y., & Sporn, M. B. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm000008j · Cited by 117
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The Synthetic Triterpenoid CDDO-Imidazolide Suppresses STAT Phosphorylation and Induces Apoptosis in Myeloma and Lung Cancer Cells
Liby, K. T., Voong, N., Williams, C. R., Risingsong, R., Royce, D. B., Honda, T., Gribble, G. W., Sporn, M. B., & Letterio, J. J. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0215 · Cited by 116
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Multicenter Phase II Study of Oral Bexarotene for Patients With Metastatic Breast Cancer
Esteva, F. J., Glaspy, J. A., Baidas, S. M., Laufman, L. R., Hutchins, L. F., Dickler, M. N., Tripathy, D., Cohen, R., DeMichele, A. M., Yocum, R. C., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.05.068 · Cited by 115
Transcriptional regulation via cysteine thiol modification: A novel molecular strategy for chemoprevention and cytoprotection
Na, H., & Surh, Y. (2006) · Molecular Carcinogenesis · doi:10.1002/mc.20225 · Cited by 111
The novel triterpenoid CDDO and its derivatives induce apoptosis by disruption of intracellular redox balance.
Ikeda, T., Sporn, M. B., Honda, T., Gribble, G. W., & Kufe, D. W. (2003) · PubMed · Cited by 111
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The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-κB activation through direct inhibition of IκB kinase β
Yore, M. M., Liby, K. T., Honda, T., Gribble, G. W., & Sporn, M. B. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0444 · Cited by 109
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Studies on the reactivity of CDDO, a promising new chemopreventive and chemotherapeutic agent: implications for a molecular mechanism of action
Couch, R. D., Browning, R. G., Honda, T., Gribble, G. W., Wright, D. L., Sporn, M. B., & Anderson, A. C. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.03.031 · Cited by 105
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2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) Directly Targets Mitochondrial Glutathione to Induce Apoptosis in Pancreatic Cancer
Samudio, I. J., Konopleva, M. Y., Hail, N., Shi, Y.-X., McQueen, T. J., Hsu, T., Evans, R. L., Honda, T., Gribble, G. W., Sporn, M. B., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507518200 · Cited by 102
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Human Immunodeficiency Virus Type 1-Induced Macrophage Gene Expression Includes the p21 Gene, a Target for Viral Regulation
Vázquez, N., Greenwell‐Wild, T., Marinos, N. J., Swaim, W. D., Nares, S., Ott, D. E., Schubert, U., Henklein, P., Orenstein, J. M., Sporn, M. B., et al. (2005) · Journal of Virology · doi:10.1128/jvi.79.7.4479-4491.2005 · Cited by 102
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A retinoid X receptor (RXR)-selective retinoid reveals that RXR-α is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands
Crowe, D. L., & Chandraratna, R. A. S. (2004) · Breast Cancer Research · doi:10.1186/bcr913 · Cited by 101
BRCA1 Transcriptionally Regulates Damaged DNA Binding Protein (DDB2) In the DNA Repair Response Following UV-Irradiation
Takimoto, R., MacLachlan, T. K., Dicker, D. T., Niitsu, Y., Mori, T., & El‐Deiry, W. S. (2002) · Cancer Biology & Therapy · doi:10.4161/cbt.65 · Cited by 92
The Novel Triterpenoid 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) Potently Enhances Apoptosis Induced by Tumor Necrosis Factor in Human Leukemia Cells
Stadheim, T. A., Suh, N., Ganju, N., Sporn, M. B., & Eastman, A. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108974200 · Cited by 91
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Synthetic triterpenoids enhance transforming growth factor beta/Smad signaling.
Suh, N., Roberts, A. B., Reffey, S. B., Miyazono, K., Itoh, S., ten Dijke, P., Heiß, E. H., Place, A. E., Risingsong, R., Williams, C. R., et al. (2003) · PubMed · Cited by 90
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Synthetic triterpenoids activate a pathway for apoptosis in AML cells involving downregulation of FLIP and sensitization to TRAIL
Suh, W.-S., Kim, Y. S., Schimmer, A. D., Kitada, S., Minden, M. D., Andreeff, M., Suh, N., Sporn, M., & Reed, J. C. (2003) · Leukemia · doi:10.1038/sj.leu.2403112 · Cited by 89
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2-Cyano-3,12-dioxoolean-1,9-dien-28-oic Acid and Related Compounds Inhibit Growth of Colon Cancer Cells through Peroxisome Proliferator-Activated Receptor γ-Dependent and -Independent Pathways
Chintharlapalli, S. R., Papineni, S., Konopleva, M. Y., Andreef, M., Samudio, I. J., & Safe, S. H. (2005) · Molecular Pharmacology · doi:10.1124/mol.105.011437 · Cited by 83
Induction of redox imbalance and apoptosis in multiple myeloma cells by the novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid
Ikeda, T., Nakata, Y., Kimura, F., Sato, K., Anderson, K. C., Motoyoshi, K., Sporn, M. B., & Kufe, D. W. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.39.3.1 · Cited by 81
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Enantioselective Syntheses of Potent Retinoid X Receptor Ligands: Differential Biological Activities of Individual Antipodes
Vuligonda, V., Thacher, S. M., & Chandraratna, R. A. S. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm0100584 · Cited by 79
TGF-β signaling in T cells: roles in lymphoid and epithelial neoplasia
Letterio, J. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208922 · Cited by 78
The Rexinoid LG100754 Is a Novel RXR:PPARγ Agonist and Decreases Glucose Levelsin Vivo
Cesario, R. M., Klausing, K., Razzaghi, H., Crombie, D. L., Rungta, D. K., Heyman, R. A., & Lala, D. S. (2001) · Molecular Endocrinology · doi:10.1210/mend.15.8.0677 · Cited by 71
Biological Characterization of a Heterodimer-Selective Retinoid X Receptor Modulator: Potential Benefits for the Treatment of Type 2 Diabetes
Leibowitz, M. D., Ardecky, R., Boehm, M. F., Broderick, C. L., Carfagna, M. A., Crombie, D. L., D’Arrigo, J., Etgen, G. J., Faul, M. M., Grese, T. A., et al. (2005) · Endocrinology · doi:10.1210/en.2005-0690 · Cited by 71
Identification of a novel synthetic triterpenoid, methyl-2-cyano-3,12-dioxooleana-1,9-dien-28-oate, that potently induces caspase-mediated apoptosis in human lung cancer cells.
Kim, K. B., Lotan, R., Yue, P., Sporn, M. B., Suh, N., Gribble, G. W., Honda, T., Wu, G. S., Hong, W. K., & Sun, S. Y. (2002) · PubMed · Cited by 70
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Synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest in HER2-overexpressing breast cancer cells
Konopleva, M. Y., Zhang, W., Shi, Y.-X., McQueen, T. J., Tsao, T., Abdelrahim, M., Munsell, M. F., Johansen, M. J., Yu, D., Madden, T. L., et al. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0350 · Cited by 70
Effect of the Retinoid X Receptor-Selective Ligand LGD1069 on Mammary Carcinoma After Tamoxifen Failure
Bischoff, E. D., Heyman, R. A., & Lamph, W. W. (1999) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/91.24.2118 · Cited by 66
The novel triterpenoid CDDO-Me suppresses MAPK pathways and promotes p38 activation in acute myeloid leukemia cells
Konopleva, M. Y., Contractor, R., Kurinna, S. M., Chen, W., Andreeff, M., & Ruvolo, P. P. (2005) · Leukemia · doi:10.1038/sj.leu.2403828 · Cited by 65
Prevention and treatment of experimental breast cancer with the combination of a new selective estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268.
Suh, N., Lamph, W. W., Glasebrook, A. L., Grese, T. A., Palkowitz, A. D., Williams, C. R., Risingsong, R., Farris, M. R., Heyman, R. A., & Sporn, M. B. (2002) · PubMed · Cited by 64
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Effects of Rexinoids on Thyrotrope Function and the Hypothalamic-Pituitary-Thyroid Axis
Sharma, V., Hays, W. R., Wood, W. M., Pugazhenthi, U., Germain, D. L. S., Bianco, A. C., Krężel, W., Chambon, P., & Haugen, B. R. (2005) · Endocrinology · doi:10.1210/en.2005-0706 · Cited by 64
The Retinoid X Receptor-Selective Retinoid, LGD1069, Down-regulates Cyclooxygenase-2 Expression in Human Breast Cells through Transcription Factor Crosstalk: Implications for Molecular-Based Chemoprevention
Kong, G., Kim, H.-T., Wu, K., DeNardo, D. G., Hilsenbeck, S. G., Xu, X.-C., Lamph, W. W., Bissonnette, R. P., Dannenberg, A. J., & Brown, P. H. (2005) · Cancer Research · doi:10.1158/0008-5472.can-03-2912 · Cited by 63
Specific Chemopreventive Agents Trigger Proteasomal Degradation of G1 Cyclins: Implications for Combination Therapy
Dragnev, K. H., Pitha, I., Ma, Y., Petty, W. J., Sekula, D., O’Sullivan-Murphy, B., Rendi, M. H., Suh, N., Desai, N. B., Sporn, M. B., et al. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0271 · Cited by 62
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The Selective Estrogen Receptor Modulator Arzoxifene and the Rexinoid LG100268 Cooperate to Promote Transforming Growth Factor β-Dependent Apoptosis in Breast Cancer
Rendi, M. H., Suh, N., Lamph, W. W., Krajewski, S., Reed, J. C., Heyman, R. A., Berchuck, A., Liby, K. T., Risingsong, R., Royce, D. B., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0234 · Cited by 60
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The Combination of the Rexinoid, LG100268, and a Selective Estrogen Receptor Modulator, Either Arzoxifene or Acolbifene, Synergizes in the Prevention and Treatment of Mammary Tumors in an Estrogen Receptor–Negative Model of Breast Cancer
Liby, K. T., Rendi, M. H., Suh, N., Royce, D. B., Risingsong, R., Williams, C. R., Lamph, W. W., Labrie, F., Krajewski, S., Xu, X., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1119 · Cited by 59
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Bexarotene and Erlotinib for Aerodigestive Tract Cancer
Dragnev, K. H., Petty, W. J., Shah, S. J., Biddle, A., Desai, N. B., Memoli, V. A., Rigas, J. R., & Dmitrovsky, E. (2005) · Journal of Clinical Oncology · doi:10.1200/jco.2005.01.9521 · Cited by 59
A novel mechanism of action of methyl-2-cyano-3,12 dioxoolean-1,9 diene-28-oate: direct permeabilization of the inner mitochondrial membrane to inhibit electron transport and induce apoptosis
Samudio, I., Konopleva, M., Pelicano, H., Huang, P., Frolova, O., Bornmann, W., Ying, Y., Evans, R., Contractor, R., & Andreeff, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.105.018051 · Cited by 58
Design, Synthesis, and Biological Evaluation of Biotin Conjugates of 2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic Acid for the Isolation of the Protein Targets
Honda, T., Janosik, T., Honda, Y., Han, J., Liby, K. T., Williams, C. R., Couch, R. D., Anderson, A. C., Sporn, M. B., & Gribble, G. W. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049727e · Cited by 56
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CDDO induces apoptosis via the intrinsic pathway in lymphoid cells
Inoue, S., Snowden, R. T., Dyer, M. J. S., & Cohen, G. M. (2004) · Leukemia · doi:10.1038/sj.leu.2403328 · Cited by 56
A selective retinoid X receptor agonist bexarotene (LGD1069, targretin) inhibits angiogenesis and metastasis in solid tumours
Yen, W.-C., Prudente, R. Y., Corpuz, M., Negro-Vilar, A. F., & Lamph, W. W. (2006) · British Journal of Cancer · doi:10.1038/sj.bjc.6602995 · Cited by 56
Predictors of outcome in patients with oligoarthritis: Results of a protocol of intraarticular corticosteroids to all clinically active joints
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Novel (2E,4E,6Z)-7-(2-Alkoxy-3,5-dialkylbenzene)-3-methylocta-2,4,6-trienoic Acid Retinoid X Receptor Modulators Are Active in Models of Type 2 Diabetes
Michellys, P., Ardecky, R., Chen, J. H., Crombie, D. L., Etgen, G. J., Faulkner, A. L., Faul, M. M., Grese, T. A., Heyman, R. A., Karanewsky, D. S., et al. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm020340q · Cited by 52
Structure-Based Design of Potent Retinoid X Receptor α Agonists
Haffner, C. D., Lenhard, J. M., Miller, A. B., McDougald, D. L., Dwornik, K. A., Ittoop, O. R. R., Robert T. Gampe, Xu, H. E., Blanchard, S., Montana, V. G., et al. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm030565g · Cited by 52
Evidence Supporting a Role for Calcium in Apoptosis Induction by the Synthetic Triterpenoid 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic Acid (CDDO)
Hail, N., Konopleva, M. Y., Sporn, M. B., Lotan, R., & Andreeff, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312758200 · Cited by 51
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Generation of mutator mutants during carcinogenesis
Venkatesan, R. N., Bielas, J. H., & Loeb, L. A. (2005) · DNA repair · doi:10.1016/j.dnarep.2005.10.012 · Cited by 49
Depletion of ntracellular Glutathione Contributes to JNK-Mediated Death Receptor 5 Upregulation and Apoptosis Induction by the Novel Synthetic Triterpenoid Methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me)1
Yue, P., Zhou, Z., Khuri, F. R., & Sun, S. (2006) · Cancer Biology & Therapy · doi:10.4161/cbt.5.5.2565 · Cited by 49
Growth-inhibitory effect of a novel synthetic triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, on ovarian carcinoma cell lines not dependent on peroxisome proliferator-activated receptor-γ expression
Melichar, B., Konopleva, M. Y., Hu, W., Melicharová, K., Andreeff, M., & Freedman, R. S. (2004) · Gynecologic Oncology · doi:10.1016/j.ygyno.2004.01.008 · Cited by 48
Design, synthesis, and anti-inflammatory activity both in vitro and in vivo of new betulinic acid analogues having an enone functionality in ring A
Honda, T., Liby, K. T., Su, X., Sundararajan, C., Honda, Y., Suh, N., Risingsong, R., Williams, C. R., Royce, D. B., Sporn, M. B., et al. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.09.012 · Cited by 48
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Isopentenoids and Other Natural Products
Nes, W. D. (1994) · ACS symposium series · doi:10.1021/bk-1994-0562 · Cited by 47
The selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced breast carcinoma
Yen, W.-C., & Lamph, W. W. (2005) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-05-0018 · Cited by 46
Synergistic effect of a retinoid X receptor-selective ligand bexarotene (LGD1069, Targretin) and paclitaxel (Taxol) in mammary carcinoma
Yen, W.-C., Prudente, R. Y., & Lamph, W. W. (2004) · Breast Cancer Research and Treatment · doi:10.1007/s10549-004-1426-5 · Cited by 46
A selective retinoid X receptor agonist bexarotene (LGD1069, Targretin) prevents and overcomes multidrug resistance in advanced prostate cancer
Yen, W.-C., & Lamph, W. W. (2005) · The Prostate · doi:10.1002/pros.20347 · Cited by 46
The triterpenoid CDDO inhibits expression of matrix metalloproteinase-1, matrix metalloproteinase-13 and Bcl-3 in primary human chondrocytes
Elliott, S. F., Hays, E., Mayor, M. B., Sporn, M. B., & Vincenti, M. P. (2003) · Arthritis Research & Therapy · doi:10.1186/ar792 · Cited by 46
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Identification of Biomarkers Modulated by the Rexinoid LGD1069 (Bexarotene) in Human Breast Cells Using Oligonucleotide Arrays
Kim, H.-T., Kong, G., DeNardo, D. G., Li, Y., Uray, I. P., Pal, S., Mohsin, S. K., Hilsenbeck, S. G., Bissonnette, R. P., Lamph, W. W., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2515 · Cited by 44
The synthetic triterpenoid CDDO-imidazolide induces monocytic differentiation by activating the Smad and ERK signaling pathways in HL60 leukemia cells
Ji, Y., Lee, H. J., Goodman, C., Uskoković, M. R., Liby, K. T., Sporn, M. B., & Suh, N. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0136 · Cited by 43
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Efficacy of Targretin on methylnitrosourea-induced mammary cancers: prevention and therapy dose-response curves and effects on proliferation and apoptosis
Lubet, R. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh338 · Cited by 40
Receptor-selective retinoids inhibit the growth of normal and malignant breast cells by inducing G1 cell cycle blockade
Wu, K., Dupre, E., Kim, H., Tin-U, C., Bissonnette, R. P., Lamph, W. W., & Brown, P. H. (2005) · Breast Cancer Research and Treatment · doi:10.1007/s10549-005-9071-1 · Cited by 39
Redox Modulation of Chemotherapy-Induced Tumor Cell Killing and Normal Tissue Toxicity
Doroshow, J. H. (2006) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djj065 · Cited by 38
Induction of adipocyte-specific gene expression is correlated with mammary tumor regression by the retinoid X receptor-ligand LGD1069 (targretin).
Agarwal, V. R., Bischoff, E. D., Hermann, T. W., & Lamph, W. W. (2000) · PubMed · Cited by 36
Suppression of human pancreatic cancer cell proliferation by AGN194204, an RXR-selective retinoid
Balasubramanian, S. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh122 · Cited by 36
Design, Synthesis, and Structure−Activity Relationship Studies of Novel 6,7-Locked-[7-(2-alkoxy-3,5-dialkylbenzene)-3-methylocta]-2,4,6-trienoic Acids
Michellys, P., Ardecky, R., Chen, J., D’Arrigo, J., Grese, T. A., Karanewsky, D. S., Leibowitz, M. D., Liu, S., Mais, D. E., Mapes, C. M., et al. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm020401k · Cited by 34
Prevention of lung cancer progression by bexarotene in mouse models
Wang, Y., Zhang, Z., Yao, R., Jia, D., Wang, D., Lubet, R. A., & You, M. (2005) · Oncogene · doi:10.1038/sj.onc.1209180 · Cited by 34
The retinoid X receptor agonist bexarotene (Targretin) synergistically enhances the growth inhibitory activity of cytotoxic drugs in non-small cell lung cancer cells
Hermann, T. W., Yen, W.-C., Tooker, P., Fan, B., Roegner, K. R., Negro-Vilar, A. F., Lamph, W. W., & Bissonnette, R. P. (2005) · Lung Cancer · doi:10.1016/j.lungcan.2005.05.008 · Cited by 34
Triterpenoids
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3 of the 175 references couldn’t be matched to a known paper.

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Suh, N. et al. Prevention and treatment of experimental breast cancer with the combination of a new selective estrogen receptor modulator, arzoxifene, and a new rexinoid, LG 100268. Clin. Cancer Res. 8, 3270–3275 (2002). The first report of the combination of a rexinoid and a SERM for prevention and treatment of breast cancer.

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Authors: Liby, K. T., Yore, M. M., & Sporn, M. B.
Affiliations: Dartmouth College (US)
Corresponding author: Sporn, Michael B.
ORCID: Liby, Karen T.
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2007-04-19
Volume: 7
Issue: 5
Pages: 357-369
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc2129
OpenAlex: W2000178617
Cited by: 637
References: 175
Citations by year: 2026: 9 · 2025: 13 · 2024: 23 · 2023: 30 · 2022: 32 · 2021: 23 · 2020: 28 · 2019: 27 · 2018: 15 · 2017: 35 · 2016: 36 · 2015: 44 · 2014: 47 · 2013: 43 · 2012: 48
FWCI: 3.46
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Chemistry › Organic Chemistry › Natural product bioactivities and synthesis
Physical Sciences › Chemistry › Organic Chemistry › Phytochemical Studies and Bioactivities
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Effects of Natural Compounds
Keywords: oleanane triterpenoids, rexinoids, cancer prevention, cancer therapy, retinoid X receptor, antiproliferative agents, apoptosis, inflammation, redox state, multi-target drugs, drug synergy
MeSH terms: Animals, Anti-Inflammatory Agents, Antineoplastic Agents, Dose-Response Relationship, Drug, Humans, Neoplasms, Oleanolic Acid, Anticarcinogenic Agents, Retinoid X Receptors, Mice

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Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer

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