| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892-4255 [J. T., L. M. D. L.], and Department of Hygienic Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142, Japan [N. T.]
The rationale for the use of all-trans-retinoic acid (RA) as an anticancer agent is based on its ability to inhibit growth and promote differentiation of some neoplastic cells. However, RA is not effective in all conditions of cell culture, and in some cases, it may stimulate cell growth. We used a serum-free culture system to study the effect of RA on cell proliferation. Following 2 days of RA exposure, 9 of a total of 15 cell lines showed an inhibition of cell growth (RA-sensitive), while 6 of 15 cell lines showed resistance to RA (RA-resistant cells). Metabolic studies and high-performance liquid chromatography analysis of the cell-associated and medium extracts from cells incubated with [3H]RA revealed that all nine RA-sensitive cells showed a very high activity to metabolize RA to polar metabolites found in the medium. In sharp contrast, RA-resistant cells retained about 60% of the original RA at 76 h. However, conditioned medium from the sensitive cells was without activity on the growth of sensitive and resistant cells. We conclude that a relationship exists between RA inhibition of cell growth and intracellular RA metabolism. These data may help design useful strategies in cancer therapy by retinoids and dispel the notion that RA itself is responsible for the inhibition of cell growth.
1 To whom requests for reprints should be addressed, at Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Building 37, Room 3A-17, 37 Convent Drive, Bethesda, MD 20892-4255.
Received 10/24/95. Accepted 12/29/95.
This article has been cited by other articles:
|
|
 |
|
  P. T. Liu, J. Phan, D. Tang, M. Kanchanapoomi, B. Hall, S. R. Krutzik, and J. Kim CD209+ Macrophages Mediate Host Defense against Propionibacterium acnes J. Immunol., April 1, 2008; 180(7): 4919 - 4923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Cifelli and A. C. Ross All-trans-retinoic acid distribution and metabolism in vitamin A-marginal rats. Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G195 - G202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Ross, N. Ambalavanan, R. Zolfaghari, and N.-q. Li Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats J. Lipid Res., August 1, 2006; 47(8): 1844 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. de Almeida Vasconcelos Fonseca, C. E. A. Chagas, R. P. Mazzantini, R. Heidor, T. P. Ong, and F. S. Moreno All-trans and 9-cis retinoic acids, retinol and {beta}-carotene chemopreventive activities during the initial phases of hepatocarcinogenesis involve distinct actions on glutathione S-transferase positive preneoplastic lesions remodeling and DNA damage Carcinogenesis, November 1, 2005; 26(11): 1940 - 1946. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ragolia, T. Palaia, E. Paric, and J. K. Maesaka Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells J. Biol. Chem., June 6, 2003; 278(24): 22175 - 22181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Simmons, F. Andreola, and L. M. De Luca Human melanomas of fibroblast and epithelial morphology differ widely in their ability to synthesize retinyl esters Carcinogenesis, November 1, 2002; 23(11): 1821 - 1830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Tibaduiza, J. C. Fleet, R. M. Russell, and N. I. Krinsky Excentric Cleavage Products of {beta}-Carotene Inhibit Estrogen Receptor Positive and Negative Breast Tumor Cell Growth In Vitro and Inhibit Activator Protein-1-Mediated Transcriptional Activation J. Nutr., June 1, 2002; 132(6): 1368 - 1375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Guo, B. S. Knudsen, D. M. Peehl, A. Ruiz, D. Bok, R. R. Rando, J. S. Rhim, D. M. Nanus, and L. J. Gudas Retinol Metabolism and Lecithin:Retinol Acyltransferase Levels Are Reduced in Cultured Human Prostate Cancer Cells and Tissue Specimens Cancer Res., March 1, 2002; 62(6): 1654 - 1661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Sun, P. Yue, G. J. Kelloff, V. E. Steele, S. M. Lippman, W. K. Hong, and R. Lotan Identification of Retinamides That Are More Potent than N-(4-Hydroxyphenyl)retinamide in Inhibiting Growth and Inducing Apoptosis of Human Head and Neck and Lung Cancer Cells Cancer Epidemiol. Biomarkers Prev., June 1, 2001; 10(6): 595 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Marill, T. Cresteil, M. Lanotte, and G. G. Chabot Identification of Human Cytochrome P450s Involved in the Formation of All-trans-Retinoic Acid Principal Metabolites Mol. Pharmacol., April 13, 2001; 58(6): 1341 - 1348. [Abstract] [Full Text]
|
|
|
|
 |
|
 I. Klaassen, R. H. Brakenhoff, S. J. Smeets, G. B. Snow, and B. J. M. Braakhuis Enhanced Turnover of all-trans-Retinoic Acid and Increased Formation of Polar Metabolites in Head and Neck Squamous Cell Carcinoma Lines Compared with Normal Oral Keratinocytes Clin. Cancer Res., April 1, 2001; 7(4): 1017 - 1025. [Abstract] [Full Text]
|
|
|
|
|
|
X. Guo, D. M Nanus, A. Ruiz, R. R Rando, D. Bok, and L. J Gudas Reduced Levels of Retinyl Esters and Vitamin A in Human Renal Cancers Cancer Res., March 1, 2001; 61(6): 2774 - 2781. [Abstract] [Full Text]
|
|
|
|
|
|
N. Idres, G. Benoît, M. A. Flexor, M. Lanotte, and G. G. Chabot Granulocytic Differentiation of Human NB4 Promyelocytic Leukemia Cells Induced by All-trans Retinoic Acid Metabolites Cancer Res., January 1, 2001; 61(2): 700 - 705. [Abstract] [Full Text]
|
|
|
|
 |
|
 A Parlesak, I Menzl, A Feuchter, J C Bode, and C Bode Inhibition of retinol oxidation by ethanol in the rat liver and colon Gut, December 1, 2000; 47(6): 825 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Schwartz Biomarkers and Molecular Epidemiology and Chemoprevention of Oral Carcinogenesis Critical Reviews in Oral Biology & Medicine, January 1, 2000; 11(1): 92 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Giandomenico, F. Andreola, M. L. R. de la Concepcion, S. J. Collins, and L. M. De Luca Retinoic acid and 4-hydroxyphenylretinamide induce growth inhibition and tissue transglutaminase through different signal transduction pathways in mouse fibroblasts (NIH 3T3 cells) Carcinogenesis, June 1, 1999; 20(6): 1133 - 1135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Neuville, Z.-q Yan, A. Gidlof, M. S. Pepper, G. K. Hansson, G. Gabbiani, and A. Sirsjo Retinoic Acid Regulates Arterial Smooth Muscle Cell Proliferation and Phenotypic Features In Vivo and In Vitro Through an RAR{alpha}-Dependent Signaling Pathway Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1430 - 1436. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Pasquali, V. Rossi, D. Prezioso, V. Gentile, V. Colantuoni, T. Lotti, A. Bellastella, and A. A. Sinisi Changes in Tissue Transglutaminase Activity and Expression during Retinoic Acid-Induced Growth Arrest and Apoptosis in Primary Cultures of Human Epithelial Prostate Cells J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1463 - 1469. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. C. Roos, F. K. Jugert, H. F. Merk, and D. R. Bickers Retinoid Metabolism in the Skin Pharmacol. Rev., June 1, 1998; 50(2): 315 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Abu-Abed, B. R. Beckett, H. Chiba, J. V. Chithalen, G. Jones, D. Metzger, P. Chambon, and M. Petkovich Mouse P450RAI (CYP26) Expression and Retinoic Acid-inducible Retinoic Acid Metabolism in F9 Cells Are Regulated by Retinoic Acid Receptor gamma and Retinoid X Receptor alpha J. Biol. Chem., January 23, 1998; 273(4): 2409 - 2415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hurnanen, H. M. Chan, and S. Kubow The Protective Effect of Metallothionein Against Lipid Peroxidation Caused by Retinoic Acid in Human Breast Cancer Cells J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1520 - 1528. [Abstract] [Full Text]
|
|
|
|
|
|
B.-j. M. van der Leede, C. E. van den Brink, W. W. M. Pijnappel, E. Sonneveld, P. T. van der Saag, and B. van der Burg Autoinduction of Retinoic Acid Metabolism to Polar Derivatives with Decreased Biological Activity in Retinoic Acid-sensitive, but Not in Retinoic Acid-resistant Human Breast Cancer Cells J. Biol. Chem., July 18, 1997; 272(29): 17921 - 17928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. White, Y.-D. Guo, K. Baetz, B. Beckett-Jones, J. Bonasoro, K. E. Hsu, F. J. Dilworth, G. Jones, and M. Petkovich Identification of the Retinoic Acid-inducible All-trans-retinoic Acid 4-Hydroxylase J. Biol. Chem., November 22, 1996; 271(47): 29922 - 29927. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
