Novel retinoid-related molecules as apoptosis inducers and effective inhibitors of human lung cancer cells in vivo - PubMed (original) (raw)
Novel retinoid-related molecules as apoptosis inducers and effective inhibitors of human lung cancer cells in vivo
X P Lu et al. Nat Med. 1997 Jun.
Abstract
Lung cancer causes more than 140,000 deaths annually in the United States alone, and the prognosis for non-small cell lung cancer (NSCLC) is particularly poor. Therapies using small molecules that preferentially kill lung tumor cells by inducing cellular suicide (apoptosis) would therefore be highly desirable. Retinoids have shown promise as cancer preventive and cancer therapeutic agents. Retinoid signals are mediated by two classes of nuclear receptors: the retinoic acid receptors (RAR alpha, beta, and gamma) and the retinoid X receptors (RXR alpha, beta and gamma). These receptors usually bind as heterodimers to specific DNA sequences and/or interact with other transcriptional regulators, such as AP-1 (ref. 10) to regulate gene transcription. Synthetic retinoids can be made that activate only specific portions of the complex retinoid response network and activate selective biological programs. To identify retinoids with novel biological activities, we used a high-throughput "biological activity fingerprint" screen on a large library of retinoids and retinoid-related molecules (RRMs). We identified new structures that are highly effective against lung cancer cells in vitro, inducing apoptosis. We show here for one of these compounds that it is very effective against a human NSCLC in vivo in an animal model. These new molecules show a distinct pattern of receptor signaling.
Similar articles
- Differential effects of synthetic nuclear retinoid receptor-selective retinoids on the growth of human non-small cell lung carcinoma cells.
Sun SY, Yue P, Dawson MI, Shroot B, Michel S, Lamph WW, Heyman RA, Teng M, Chandraratna RA, Shudo K, Hong WK, Lotan R. Sun SY, et al. Cancer Res. 1997 Nov 1;57(21):4931-9. Cancer Res. 1997. PMID: 9354460 - Identification of receptor-selective retinoids that are potent inhibitors of the growth of human head and neck squamous cell carcinoma cells.
Sun SY, Yue P, Mao L, Dawson MI, Shroot B, Lamph WW, Heyman RA, Chandraratna RA, Shudo K, Hong WK, Lotan R. Sun SY, et al. Clin Cancer Res. 2000 Apr;6(4):1563-73. Clin Cancer Res. 2000. PMID: 10778990 - Receptor-selective retinoid agonists and teratogenic activity.
Willhite CC, Dawson MI, Reichert U. Willhite CC, et al. Drug Metab Rev. 1996 Feb-May;28(1-2):105-19. doi: 10.3109/03602539608993994. Drug Metab Rev. 1996. PMID: 8744592 Review. - Cyclin proteolysis as a retinoid cancer prevention mechanism.
Dragnev KH, Freemantle SJ, Spinella MJ, Dmitrovsky E. Dragnev KH, et al. Ann N Y Acad Sci. 2001 Dec;952:13-22. doi: 10.1111/j.1749-6632.2001.tb02724.x. Ann N Y Acad Sci. 2001. PMID: 11795432 Review.
Cited by
- Inhibition of IkappaB kinase by a new class of retinoid-related anticancer agents that induce apoptosis.
Bayon Y, Ortiz MA, Lopez-Hernandez FJ, Gao F, Karin M, Pfahl M, Piedrafita FJ. Bayon Y, et al. Mol Cell Biol. 2003 Feb;23(3):1061-74. doi: 10.1128/MCB.23.3.1061-1074.2003. Mol Cell Biol. 2003. PMID: 12529410 Free PMC article. - Adamantyl-substituted retinoid-related molecules bind small heterodimer partner and modulate the Sin3A repressor.
Farhana L, Dawson MI, Leid M, Wang L, Moore DD, Liu G, Xia Z, Fontana JA. Farhana L, et al. Cancer Res. 2007 Jan 1;67(1):318-25. doi: 10.1158/0008-5472.CAN-06-2164. Cancer Res. 2007. PMID: 17210713 Free PMC article. - Retinoic acid receptor gamma1 (RARgamma1) levels control RARbeta2 expression in SK-N-BE2(c) neuroblastoma cells and regulate a differentiation-apoptosis switch.
Ferrari N, Pfahl M, Levi G. Ferrari N, et al. Mol Cell Biol. 1998 Nov;18(11):6482-92. doi: 10.1128/MCB.18.11.6482. Mol Cell Biol. 1998. PMID: 9774664 Free PMC article. - Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells.
Hammond LA, Van Krinks CH, Durham J, Tomkins SE, Burnett RD, Jones EL, Chandraratna RA, Brown G. Hammond LA, et al. Br J Cancer. 2001 Aug 3;85(3):453-62. doi: 10.1054/bjoc.2001.1939. Br J Cancer. 2001. PMID: 11487280 Free PMC article. - All-trans-retinoic acid induces apoptosis in Leydig cells via activation of the mitochondrial death pathway and antioxidant enzyme regulation.
Tucci P, Cione E, Perri M, Genchi G. Tucci P, et al. J Bioenerg Biomembr. 2008 Aug;40(4):315-23. doi: 10.1007/s10863-008-9156-8. Epub 2008 Jul 31. J Bioenerg Biomembr. 2008. PMID: 18668354
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical