Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

Crossref logo

Fol. Biol. 2007, 53, 37-49

https://doi.org/10.14712/fb2007053020037

Valproic Acid, a Molecular Lead to Multiple Regulatory Pathways

M. Kostrouchová1, Z. Kostrouch1, Marta Kostrouchová2

1Laboratory of Molecular Pathology, Institute of Inherited Metabolic Disorders of the 1st Faculty of Medicine, Charles University, Prague, Czech Republic
2Laboratory of Molecular Biology and Genetics, Institute of Inherited Metabolic Disorders of the 1st Faculty of Medicine, Charles University, Prague, Czech Republic

Received February 2007
Accepted March 2007

References

1. Altucci, L., Clarke, N., Nebbioso, A., Scognamiglio, A., Gronemeyer, H. (2005) Acute myeloid leukemia: therapeutic impact of epigenetic drugs. Int. J. Biochem. Cell. Biol. 37, 1752-1762. <https://doi.org/10.1016/j.biocel.2005.04.019>
2. Angelucci, A., Valentini, A., Millimaggi, D., Gravina, G. L., Miano, R., Dolo, V., Vicentini, C., Bologna, M., Federici, G., Bernardini, S. (2006) Valproic acid induces apoptosis in prostate carcinoma cell lines by activation of multiple death pathways. Anticancer Drugs 17, 1141-1150. <https://doi.org/10.1097/01.cad.0000236302.89843.fc>
3. Annicotte, J. S., Iankova, I., Miard, S., Fritz, V., Sarruf, D., Abella, A., Berthe, M. L., Noel, D., Pillon, A., Iborra, F., Dubus, P., Maudelonde, T., Culine, S., Fajas, L. (2006) Peroxisome proliferator-activated receptor γ regulates E-cadherin expression and inhibits growth and invasion of prostate cancer. Mol. Cell. Biol. 26, 7561-7574. <https://doi.org/10.1128/MCB.00605-06>
4. Armeanu, S., Bitzer, M., Lauer, U. M., Venturelli, S., Pathil, A., Krusch, M., Kaiser, S., Jobst, J., Smirnow, I., Wagner, A., Steinle, A., Salih, H. R. (2005a) Natural killer cell-mediated lysis of hepatoma cells via specific induction of NKG2D ligands by the histone deacetylase inhibitor sodium valproate. Cancer Res. 65, 6321-6329. <https://doi.org/10.1158/0008-5472.CAN-04-4252>
5. Armeanu, S., Pathil, A., Venturelli, S., Mascagni, P., Weiss, T. S., Gottlicher, M., Gregor, M., Lauer, U. M., Bitzer, M. (2005b) Apoptosis on hepatoma cells but not on primary hepatocytes by histone deacetylase inhibitors valproate and ITF2357. J. Hepatol. 42, 210-217. <https://doi.org/10.1016/j.jhep.2004.10.020>
6. Asghari, V., Wang, J. F., Reiach, J. S., Young, L. T. (1998) Differential effects of mood stabilizers on Fos/Jun proteins and AP-1 DNA binding activity in human neuroblastoma SH-SY5Y cells. Brain. Res. Mol. Brain Res. 58, 95-102. <https://doi.org/10.1016/S0169-328X(98)00107-7>
7. Balbi, A., Sottofattori, E., Mazzei, M., Sannita, W. G. (1991) Study of bioequivalence of magnesium and sodium valproates. J. Pharm. Biomed. Anal. 9, 317-321. <https://doi.org/10.1016/0731-7085(91)80200-S>
8. Bienz, M. (2005) β-Catenin: a pivot between cell adhesion and Wnt signalling. Curr. Biol. 15, R64-67. <https://doi.org/10.1016/j.cub.2004.12.058>
9. Bienz, M., Clevers, H. (2000) Linking colorectal cancer to Wnt signaling. Cell 103, 311-320. <https://doi.org/10.1016/S0092-8674(00)00122-7>
10. Bjorge, S. M., Baillie, T. A. (1991) Studies on the β-oxidation of valproic acid in rat liver mitochondrial preparations. Drug Metab. Dispos. 19, 823-829.
11. Blaheta, R. A., Cinatl, J., Jr. (2002) Anti-tumor mechanisms of valproate: a novel role for an old drug. Med. Res. Rev. 22, 492-511. <https://doi.org/10.1002/med.10017>
12. Blaheta, R. A., Nau, H., Michaelis, M., Cinatl, J., Jr. (2002) Valproate and valproate-analogues: potent tools to fight against cancer. Curr. Med. Chem. 9, 1417-1433. <https://doi.org/10.2174/0929867023369763>
13. Blaheta, R. A., Michaelis, M., Driever, P. H., Cinatl, J., Jr. (2005) Evolving anticancer drug valproic acid: insights into the mechanism and clinical studies. Med. Res. Rev. 25, 383-397. <https://doi.org/10.1002/med.20027>
14. Bojic, U., Ehlers, K., Ellerbeck, U., Bacon, C. L., O’Driscoll, E., O’Connell, C., Berezin, V., Kawa, A., Lepekhin, E., Bock, E., Regan, C. M., Nau, H. (1998) Studies on the teratogen pharmacophore of valproic acid analogues: evidence of interactions at a hydrophobic centre. Eur. J. Pharmacol. 354, 289-299. <https://doi.org/10.1016/S0014-2999(98)00462-2>
15. Bowden, C. L., Singh, V. (2005) Valproate in bipolar disorder: 2000 onwards. Acta Psychiatr. Scand. 111, 13-20. <https://doi.org/10.1111/j.1600-0447.2005.00522.x>
16. Brown, D., Kogan, S., Lagasse, E., Weissman, I., Alcalay, M., Pelicci, P. G., Atwater, S., Bishop, J. M. (1997) A PMLRARα transgene initiates murine acute promyelocytic leukemia. Proc. Natl. Acad. Sci. USA 94, 2551-2556. <https://doi.org/10.1073/pnas.94.6.2551>
17. Bruserud, O., Stapnes, C., Tronstad, K. J., Ryningen, A., Anensen, N., Gjertsen, B. T. (2006) Protein lysine acetylation in normal and leukaemic haematopoiesis: HDACs as possible therapeutic targets in adult AML. Expert. Opin. Ther. Targets 10, 51-68. <https://doi.org/10.1517/14728222.10.1.51>
18. Brush, M. H., Guardiola, A., Connor, J. H., Yao, T. P., Shenolikar, S. (2004) Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases. J. Biol. Chem. 279, 7685-7691. <https://doi.org/10.1074/jbc.M310997200>
19. Bug, G., Ritter, M., Wassmann, B., Schoch, C., Heinzel, T., Schwarz, K., Romanski, A., Kramer, O. H., Kampfmann, M., Hoelzer, D., Neubauer, A., Ruthardt, M., Ottmann, O. G. (2005) Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia. Cancer 104, 2717-2725. <https://doi.org/10.1002/cncr.21589>
20. Burton, B. S. (1882) On the propyl derivatives and decomposition products of ethylacetoacetate. Am. Chem. J. 3, 385-395.
21. Catalano, M. G., Fortunati, N., Pugliese, M., Costantino, L., Poli, R., Bosco, O., Boccuzzi, G. (2005) Valproic acid induces apoptosis and cell cycle arrest in poorly differentiated thyroid cancer cells. J. Clin. Endocrinol. Metab. 90, 1383-1389. <https://doi.org/10.1210/jc.2004-1355>
22. Chang, T. H., Szabo, E. (2002) Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-γ and inhibitors of histone deacetylase in adenocarcinoma of the lung. Clin. Cancer Res. 8, 1206-1212.
23. Chen, C. S., Weng, S. C., Tseng, P. H, Lin, H. P. (2005) Histone acetylation-independent effect of histone deacetylase inhibitors on Akt through the reshuffling of protein phosphatase 1 complexes. J. Biol. Chem. 280, 38879-38887. <https://doi.org/10.1074/jbc.M505733200>
24. Chen, G., Yuan, P., Hawver, D. B., Potter, W. Z., Manji, H. K. (1997) Increase in AP-1 transcription factor DNA binding activity by valproic acid. Neuropsychopharmacology 16, 238-245.
25. Chen, G., Huang, L. D., Jiang, Y. M., Manji, H. K. (1999a) The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3. J. Neurochem. 72, 1327-1330. <https://doi.org/10.1046/j.1471-4159.2000.0721327.x>
26. Chen, G., Yuan, P. X., Jiang, Y. M., Huang, L. D., Manji, H. K. (1999b) Valproate robustly enhances AP-1 mediated gene expression. Brain Res. Mol. Brain Res. 64, 52-58. <https://doi.org/10.1016/S0169-328X(98)00303-9>
27. Chetcuti, A., Adams, L. J., Mitchell, P. B., Schofield, P. R. (2006) Altered gene expression in mice treated with the mood stabilizer sodium valproate. Int. J. Neuropsychopharmacol. 9, 267-276. <https://doi.org/10.1017/S1461145705005717>
28. Christiansen, J. H., Coles, E. G., Wilkinson, D. G. (2000) Molecular control of neural crest formation, migration and differentiation. Curr. Opin. Cell Biol. 12, 719-724. <https://doi.org/10.1016/S0955-0674(00)00158-7>
29. Cinatl, J., Jr., Cinatl, J., Scholz, M., Driever, P. H., Henrich, D., Kabickova, H., Vogel, J. U., Doerr, H. W., Kornhuber, B. (1996) Antitumor activity of sodium valproate in cultures of human neuroblastoma cells. Anticancer Drugs 7, 766-773. <https://doi.org/10.1097/00001813-199609000-00008>
30. Cinatl, J., Jr., Cinatl, J., Driever, P. H., Kotchetkov, R., Pouckova, P., Kornhuber, B., Schwabe, D. (1997) Sodium valproate inhibits in vivo growth of human neuroblastoma cells. Anticancer Drugs 8, 958-963. <https://doi.org/10.1097/00001813-199711000-00007>
31. Cinatl, J., Jr., Kotchetkov, R., Blaheta, R., Driever, P. H., Vogel, J. U., Cinatl, J. (2002) Induction of differentiation and suppression of malignant phenotype of human neuroblastoma BE(2)-C cells by valproic acid: enhancement by combination with interferon-α. Int. J. Oncol. 20, 97-106.
32. Clarke, N., Jimenez-Lara, A. M., Voltz, E., Gronemeyer, H. (2004) Tumor suppressor IRF-1 mediates retinoid and interferon anticancer signaling to death ligand TRAIL. EMBO J. 23, 3051-3060. <https://doi.org/10.1038/sj.emboj.7600302>
33. Deutsch, J., Rapoport, S. I., Rosenberger, T. A. (2003) Valproyl-CoA and esterified valproic acid are not found in brains of rats treated with valproic acid, but the brain concentrations of CoA and acetyl-CoA are altered. Neurochem. Res. 28, 861-866. <https://doi.org/10.1023/A:1023267224819>
34. Digel, W., Lubbert, M. (2005) DNA methylation disturbances as novel therapeutic target in lung cancer: preclinical and clinical results. Crit. Rev. Oncol. Hematol. 55, 1-11. <https://doi.org/10.1016/j.critrevonc.2005.02.002>
35. Ehlers, K., Sturje, H., Merker, H. J., Nau, H. (1992) The valproic acid metabolite E-2-n-propyl-2-pentenoic acid does not induce spina bifida in the mouse. Dev. Pharmacol. Ther. 19, 196-204. <https://doi.org/10.1159/000457485>
36. Eickholt, B. J., Towers, G. J., Ryves, W. J., Eikel, D., Adley, K., Ylinen, L. M., Chadborn, N. H., Harwood, A. J., Nau, H., Williams, R. S. (2005) Effects of valproic acid derivatives on inositol trisphosphate depletion, teratogenicity, glycogen synthase kinase-3β inhibition, and viral replication: a screening approach for new bipolar disorder drugs derived from the valproic acid core structure. Mol. Pharmacol. 67, 1426-1433. <https://doi.org/10.1124/mol.104.009308>
37. Engl, T., Natsheh, I., Muller, I., Beecken, W. D., Jonas, D., Blaheta, R. A. (2004) Valproic acid induces expression of neutrophil chemoattractants of the CXC chemokine family in endothelial cells. Int. J. Clin. Pharmacol. Ther. 42, 568-574. <https://doi.org/10.5414/CPP42568>
38. Gobbi, G., Janiri, L. (2006) Sodium- and magnesium-valproate in vivo modulate glutamatergic and GABAergic synapses in the medial prefrontal cortex. Psychopharmacology (Berl.) 185, 255-262. <https://doi.org/10.1007/s00213-006-0317-3>
39. Gottlicher, M., Minucci, S., Zhu, P., Kramer, O. H., Schimpf, A., Giavara, S., Sleeman, J. P., Lo Coco, F., Nervi, C., Pelicci, P. G., Heinzel, T. (2001) Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J. 20, 6969-6978. <https://doi.org/10.1093/emboj/20.24.6969>
40. Grisolano, J. L., Wesselschmidt, R. L., Pelicci, P. G., Ley, T. J. (1997) Altered myeloid development and acute leukemia in transgenic mice expressing PML-RAR α under control of cathepsin G regulatory sequences. Blood 89, 376-387. <https://doi.org/10.1182/blood.V89.2.376>
41. Gudermann, T., Grosse, R., Schultz, G. (2000) Contribution of receptor/G protein signaling to cell growth and transformation. Naunyn Schmiedebergs Arch. Pharmacol. 361, 345-362. <https://doi.org/10.1007/s002109900208>
42. Guel, H., Wassmann, B., Romanski, A., Hoelzer, D., Ruthardt, M., Ottmann, O. G., Bug, G. (2003) Effect of the histone deacetylase inhibitor valproic acid in combination with all-trans retinoic acid on malignant hematopoiesis. Blood 102.
43. Gurvich, N., Tsygankova, O. M., Meinkoth, J. L., Klein, P.S. (2004) Histone deacetylase is a target of valproic acid-mediated cellular differentiation. Cancer Res. 64, 1079-1086. <https://doi.org/10.1158/0008-5472.CAN-03-0799>
44. Gurvich, N., Berman, M. G., Wittner, B. S., Gentleman, R. C., Klein, P. S., Green, J. B. (2005) Association of valproate-induced teratogenesis with histone deacetylase inhibition in vivo. FASEB J. 19, 1166-1168. <https://doi.org/10.1096/fj.04-3425fje>
45. Heibert, S. W., Lutterbach, B., Durst, K., Wang, L., Linggi, B., Wu, S., Wood, L., Amann, J., King, D., Hou, Y. (2001) Mechanisms of transcriptional repression by the t(8; 21)-, t(12; 21)-, and inv(16)-encoded fusion proteins. Cancer Chemother. Pharmacol. 48, S31-34. <https://doi.org/10.1007/s002800100302>
46. Hoffmann, K., Brosch, G., Loidl, P., Jung, M. (2000) First non-radioactive assay for in vitro screening of histone deacetylase inhibitors. Pharmazie 55, 601-606.
47. Insinga, A., Monestiroli, S., Ronzoni, S., Carbone, R., Pearson, M., Pruneri, G., Viale, G., Appella, E., Pelicci, P., Minucci, S. (2004) Impairment of p53 acetylation, stability and function by an oncogenic transcription factor. EMBO J. 23, 1144-1154. <https://doi.org/10.1038/sj.emboj.7600109>
48. Insinga, A., Pelicci, P. G., Inucci, S. (2005) Leukemia-associated fusion proteins. Multiple mechanisms of action to drive cell transformation. Cell Cycle 4, 67-69. <https://doi.org/10.4161/cc.4.1.1400>
49. Johannessen, C. U. (2000) Mechanisms of action of valproate: a commentatory. Neurochem. Int. 37, 103-110. <https://doi.org/10.1016/S0197-0186(00)00013-9>
50. Johannessen, C. U. Johannessen, S. I. (2003) Valproate: past, present, and future. CNS Drug Rev. 9, 199-216. <https://doi.org/10.1111/j.1527-3458.2003.tb00249.x>
51. Kaiser, M., Zavrski, I., Sterz, J., Jakob, C., Fleissner, C., Kloetzel, P. M., Sezer, O., Heider, U. (2006) The effects of the histone deacetylase inhibitor valproic acid on cell cycle, growth suppression and apoptosis in multiple myeloma. Haematologica 91, 248-251.
52. Kaneko, F., Saito, H., Saito, Y., Wakabayashi, K., Nakamoto, N., Tada, S., Suzuki, H., Tsunematsu, S., Kumagai, N., Ishii, H. (2004) Down-regulation of matrix-invasive potential of human liver cancer cells by type I interferon and a histone deacetylase inhibitor sodium butyrate. Int. J. Oncol. 24, 837-845.
53. Kawagoe, R., Kawagoe, H., Sano, K. (2002) Valproic acid induces apoptosis in human leukemia cells by stimulating both caspase-dependent and -independent apoptotic signaling pathways. Leuk. Res. 26, 495-502. <https://doi.org/10.1016/S0145-2126(01)00151-5>
54. Kawai, Y., Arinze, I. J. (2006) Valproic acid-induced gene expression through production of reactive oxygen species. Cancer Res. 66, 6563-6569. <https://doi.org/10.1158/0008-5472.CAN-06-0814>
55. Koch, A., Waha, A., Tonn, J. C., Sorensen, N., Berthold, F., Wolter, M., Reifenberger, J., Hartmann, W., Friedl, W., Reifenberger, G., Wiestler, O. D., Pietsch, T. (2001) Somatic mutations of WNT/wingless signaling pathway components in primitive neuroectodermal tumors. Int. J. Cancer 93, 445-449. <https://doi.org/10.1002/ijc.1342>
56. Koren, G., Kennedy, D. (1999) Safe use of valproic acid during pregnancy. Can. Fam. Physician 45, 1451-1453.
57. Koren, G., Nava-Ocampo, A. A., Moretti, M. E., Sussman, R., Nulman, I. (2006) Major malformations with valproic acid. Can. Fam. Physician 52, 441-442, 444, 447.
58. Kramer, O. H., Gottlicher, M., Heinzel, T. (2001) Histone deacetylase as a therapeutic target. Trends Endocrinol. Metab. 12, 294-300. <https://doi.org/10.1016/S1043-2760(01)00438-6>
59. Kramer, O. H., Zhu, P., Ostendorff, H. P., Golebiewski, M., Tiefenbach, J., Peters, M. A., Brill, B., Groner, B., Bach, I., Heinzel, T., Gottlicher, M. (2003) The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J. 22, 3411-3420. <https://doi.org/10.1093/emboj/cdg315>
60. Kuendgen, A., Schmid, M., Schlenk, R., Knipp, S., Hildebrandt, B., Steidl, C., Germing, U., Haas, R., Dohner, H., Gattermann, N. (2006) The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia. Cancer 106, 112-119. <https://doi.org/10.1002/cncr.21552>
61. Lammer, E. J., Sever, L. E., Oakley, G. P., Jr. (1987) Teratogen update: valproic acid. Teratology 35, 465-473. <https://doi.org/10.1002/tera.1420350319>
62. Lampen, A., Carlberg, C., Nau, H. (2001) Peroxisome proliferator-activated receptor δ is a specific sensor for teratogenic valproic acid derivatives. Eur. J. Pharmacol. 431, 25-33. <https://doi.org/10.1016/S0014-2999(01)01423-6>
63. Lampen, A., Siehler, S., Ellerbeck, U., Gottlicher, M., Nau, H. (1999) New molecular bioassays for the estimation of the teratogenic potency of valproic acid derivatives in vitro: activation of the peroxisomal proliferator-activated receptor (PPARδ). Toxicol. Appl. Pharmacol. 160, 238-249. <https://doi.org/10.1006/taap.1999.8770>
64. Lin, H. Y., Chen, C. S., Lin, S. P., Weng, J. R. (2006) Targeting histone deacetylase in cancer therapy. Med. Res. Rev. 26, 397-413. <https://doi.org/10.1002/med.20056>
65. Manev, H., Uz, T., Sugaya, K., Qu, T. (2000) Putative role of neuronal 5-lipoxygenase in an aging brain. FASEB J. 14, 1464-1469.
66. Manji, H. K., Chen, G., Hsiao, J. K., Risby, E. D., Masana, M. I., Potter, W. Z. (1996) Regulation of signal transduction pathways by mood-stabilizing agents: implications for the delayed onset of therapeutic efficacy. J. Clin. Psychiatry 57, 34-47.
67. Martin, M. L., Regan, C. M. (1991) The anticonvulsant valproate teratogen restricts the glial cell cycle at a defined point in the mid-G1 phase. Brain Res. 554, 223-228. <https://doi.org/10.1016/0006-8993(91)90193-Y>
68. McGarry, L. C., Winnie, J. N., Ozanne, B. W. (2004) Invasion of v-Fos(FBR)-transformed cells is dependent upon histone deacetylase activity and suppression of histone deacetylase regulated genes. Oncogene 23, 5284-5292. <https://doi.org/10.1038/sj.onc.1207687>
69. Melnick, A., Licht, J. D. (2002) Histone deacetylases as therapeutic targets in hematologic malignancies. Curr. Opin. Hematol. 9, 322-332. <https://doi.org/10.1097/00062752-200207000-00010>
70. Menegola, E., Broccia, M. L., Nau, H., Prati, M., Ricolfi, R., Giavini, E. (1996) Teratogenic effects of sodium valproate in mice and rats at midgestation and at term. Teratog. Carcinog. Mutagen 16, 97-108. <https://doi.org/10.1002/(SICI)1520-6866(1996)16:2<97::AID-TCM4>3.0.CO;2-A>
71. Menegola, E., Broccia, M. L., Prati, M., Giavini, E. (1998) Stage-dependent skeletal malformations induced by valproic acid in rat. Int. J. Dev. Biol. 42, 99-102.
72. Meunier, H., Carraz, G., Neunier, Y., Eymard, P., Aimard, M. (1963) Pharmacodynamic properties of dipropylacetic acid. 1st memory: anti-epileptic properties. Therapie 18, 435-438. (in French)
73. Michaelis, M., Michaelis, U. R., Fleming, I., Suhan, T., Cinatl, J., Blaheta, R. A., Hoffmann, K., Kotchetkov, R., Busse, R., Nau, H., Cinatl, J. Jr. (2004a) Valproic acid inhibits angiogenesis in vitro and in vivo. Mol. Pharmacol. 65, 520-527. <https://doi.org/10.1124/mol.65.3.520>
74. Michaelis, M., Suhan, T., Cinatl, J., Driever, P. H., Cinatl, J., Jr. (2004b) Valproic acid and interferon-α synergistically inhibit neuroblastoma cell growth in vitro and in vivo. Int. J. Oncol. 25, 1795-1799.
75. Mielnicki, L. M., Asch, H. L., Asch, B. B. (2001) Genes, chromatin, and breast cancer: an epigenetic tale. J. Mammary Gland Biol. Neoplasia 6, 169-182. <https://doi.org/10.1023/A:1011356623442>
76. Miller, J. R. (2002) The Wnts. Genome Biol. 31-15.
77. Miller, J. R., Hocking, A. M., Brown, J. D., Moon, R. T. (1999) Mechanism and function of signal transduction by the Wnt/β-catenin and Wnt/Ca2+ pathways. Oncogene 18, 7860-7872. <https://doi.org/10.1038/sj.onc.1203245>
78. Miller, L. D., Park, K. S., Guo, Q. M., Alkharouf, N. W., Malek, R. L., Lee, N. H., Liu, E. T., Cheng, S. Y. (2001) Silencing of Wnt signaling and activation of multiple metabolic pathways in response to thyroid hormone-stimulated cell proliferation. Mol. Cell. Biol. 21, 6626-6639. <https://doi.org/10.1128/MCB.21.19.6626-6639.2001>
79. Minucci, S., Pelicci, P. G. (1999) Retinoid receptors in health and disease: co-regulators and the chromatin connection. Semin. Cell. Dev. Biol. 10, 215-225. <https://doi.org/10.1006/scdb.1999.0303>
80. Minucci, S., Pelicci, P. G. (2006) Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat. Rev. Cancer 6, 38-51. <https://doi.org/10.1038/nrc1779>
81. Minucci, S., Maccarana, M., Cioce, M., De Luca, P., Gelmetti, V., Segalla, S., Di Croce, L., Giavara, S., Matteucci, C., Gobbi, A., Bianchini, A., Colombo, E., Schiavoni, I., Badaracco, G., Hu, X., Lazar, M. A., Landsberger, N., Nervi, C., Pelicci, P. G. (2000) Oligomerization of RAR and AML1 transcription factors as a novel mechanism of oncogenic activation. Mol. Cell 5, 811-820. <https://doi.org/10.1016/S1097-2765(00)80321-4>
82. Nau, H., Hauck, R. S., Ehlers, K. (1991) Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Pharmacol. Toxicol. 69, 310-321. <https://doi.org/10.1111/j.1600-0773.1991.tb01303.x>
83. Nebbioso, A., Clarke, N., Voltz, E., Germain, E., Ambrosino, C., Bontempo, P., Alvarez, R., Schiavone, E. M., Ferrara, F., Bresciani, F., Weisz, A., de Lera, A. R., Gronemeyer, H., Altucci, L. (2005) Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat. Med. 11, 77-84. <https://doi.org/10.1038/nm1161>
84. Oberndorfer, S., Piribauer, M., Marosi, C., Lahrmann, H., Hitzenberger, P., Grisold, W. (2005) P450 enzyme inducing and non-enzyme inducing antiepileptics in glioblastoma patients treated with standard chemotherapy. J. Neurooncol. 72, 255-260. <https://doi.org/10.1007/s11060-004-2338-2>
85. Ohira, T., Gemmill, R. M., Ferguson, K., Kusy, S., Roche, J., Brambilla, E., Zeng, C., Baron, A., Bemis, L., Erickson, P., Wilder, E., Rustgi, A., Kitajewski, J., Gabrielson, E., Bremnes, R., Franklin, W., Drabkin, H. A. (2003) WNT7a induces E-cadherin in lung cancer cells. Proc. Natl. Acad. Sci. USA 100, 10429-10434. <https://doi.org/10.1073/pnas.1734137100>
86. Okada, A., Fujiwara, M. (2006) Molecular approaches to developmental malformations using analogous forms of valproic acid. Congenit. Anom. (Kyoto), 46, 68-75. <https://doi.org/10.1111/j.1741-4520.2006.00105.x>
87. Okada, A., Aoki, Y., Kushima, K., Kurihara, H., Bialer, M., Fujiwara, M. (2004) Polycomb homologs are involved in teratogenicity of valproic acid in mice. Birth Defects Res. A. Clin. Mol. Teratol. 70, 870-879. <https://doi.org/10.1002/bdra.20085>
88. O’Loinsigh, E. D., Gherardini, L. M., Gallagher, H. C., Foley, A. G., Murphy, K. J., Regan, C. M. (2004) Differential enantioselective effects of pentyl-4-yn-valproate on spatial learning in the rat, and neurite outgrowth and cyclin D3 expression in vitro. J. Neurochem. 88, 370-379. <https://doi.org/10.1111/j.1471-4159.2004.02158.x>
89. Owens, M. J., Nemeroff, C. B. (2003) Pharmacology of valproate. Psychopharmacol. Bull. 37, 17-24.
90. Patel, L., Pass, I., Coxon, P., Downes, C. P., Smith, S. A., Macphee, C. (2001) Tumor suppressor and anti-inflammatory actions of PPARγ agonists are mediated via upregulation of PTEN. Curr. Biol. 11, 764-768. <https://doi.org/10.1016/S0960-9822(01)00225-1>
91. Phiel, C. J., Zhang, F., Huang, E. Y., Guenther, M. G., Lazar, M. A., Klein, P. S. (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J. Biol. Chem. 276, 36734-36741. <https://doi.org/10.1074/jbc.M101287200>
92. Phillips, A., Bullock, T., Plant, N. (2003) Sodium valproate induces apoptosis in the rat hepatoma cell line, FaO. Toxicology 192, 219-227. <https://doi.org/10.1016/S0300-483X(03)00331-7>
93. Pilatrino, C., Cilloni, D., Messa, E., Morotti, A., Giugliano, E., Pautasso, M., Familiari, U., Cappia, S., Pelicci, P. G., Lo Coco, F., Saglio, G., Guerrasio, A. (2005) Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid. Cancer 104, 101-109. <https://doi.org/10.1002/cncr.21132>
94. Qu, T., Uz, T., Manev, H. (2000) Inflammatory 5-LOX mRNA and protein are increased in brain of aging rats. Neurobiol. Aging 21, 647-652. <https://doi.org/10.1016/S0197-4580(00)00167-6>
95. Raffoux, E., Chaibi, P., Dombret, H., Degos, L. (2005) Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia. Haematologica 90, 986-988.
96. Regan, C. M. (1985) Therapeutic levels of sodium valproate inhibit mitotic indices in cells of neural origin. Brain Res. 347, 394-398. <https://doi.org/10.1016/0006-8993(85)90207-0>
97. Rezacova, M., Vavrova, J., Vokurkova, D., Zaskodova, D. (2006) Effect of valproic acid and antiapoptotic cytokines on differentiation and apoptosis induction of human leukemia cells. Gen. Physiol. Biophys. 25, 65-79.
98. Rocchi, P., Tonelli, R., Camerin, C., Purgato, S., Fronza, R., Bianucci, F., Guerra, F., Pession, A., Ferreri, A. M. (2005) p21Waf1/Cip1 is a common target induced by short-chain fatty acid HDAC inhibitors (valproic acid, tributyrin and sodium butyrate) in neuroblastoma cells. Oncol. Rep. 13, 1139-1144.
99. Searles, C. D., Slesinger, P. A., Singer, H. S. (1988) Effects of anticonvulsants on cholinergic and GABAergic properties in the neuronal cell clone NG108-15. Neurochem. Res. 13, 1007-1013. <https://doi.org/10.1007/BF00970776>
100. Shen, W. T., Wong, T. S., Chung, W. Y., Wong, M. G., Kebebew, E., Duh, Q. Y., Clark, O. H. (2005) Valproic acid inhibits growth, induces apoptosis, and modulates apoptosis-regulatory and differentiation gene expression in human thyroid cancer cells. Surgery 138, 979-984. <https://doi.org/10.1016/j.surg.2005.09.019>
101. Skladchikova, G., Berezin, V., Bock, E. (1998) Valproic acid, but not its non-teratogenic analogue 2-isopropylpentanoic acid, affects proliferation, viability and neuronal differentiation of the human teratocarcinoma cell line NTera-2. Neurotoxicology 19, 357-370.
102. Slesinger, P. A., Singer, H. S. (1987) Effects of anticonvulsants on cell growth and enzymatic and receptor binding activity in a neuroblastoma x glioma hybrid cell culture. Epilepsia 28, 214-221. <https://doi.org/10.1111/j.1528-1157.1987.tb04210.x>
103. Takai, N., Desmond, J. C., Kumagai, T., Gui, D., Said, J. W., Whittaker, S., Miyakawa, I., Koeffler, H. P. (2004) Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells. Clin. Cancer Res. 10, 1141-1149. <https://doi.org/10.1158/1078-0432.CCR-03-0100>
104. Tang, R., Faussat, A. M., Majdak, P., Perrot, J. Y., Chaoui, D., Legrand, O., Marie, J. P. (2004a) Valproic acid inhibits proliferation and induces apoptosis in acute myeloid leukemia cells expressing P-gp and MRP1. Leukemia 18, 1246-1251. <https://doi.org/10.1038/sj.leu.2403390>
105. Tang, Y., Glauser, T. A., Gilbert, D. L., Hershey, A. D., Privitera, M. D., Ficker, D. M., Szaflarski, J. P., Sharp, F. R. (2004b) Valproic acid blood genomic expression patterns in children with epilepsy – a pilot study. Acta Neurol. Scand. 109, 159-168. <https://doi.org/10.1046/j.1600-0404.2003.00253.x>
106. Taylor, C. T., Furuta, G. T., Synnestvedt, K., Colgan, S. P. (2000) Phosphorylation-dependent targeting of cAMP response element binding protein to the ubiquitin/proteasome pathway in hypoxia. Proc. Natl. Acad. Sci. USA, 97, 12091-12096. <https://doi.org/10.1073/pnas.220211797>
107. Toker, A. (2000) Protein kinases as mediators of phosphoinositide 3-kinase signaling. Mol Pharmacol. 57, 652-658. <https://doi.org/10.1016/S0026-895X(24)26463-4>
108. Vincan, E., Leet, C. S., Reyes, N. I., Dilley, R. J., Thomas, R. J., Phillips, W. A. (2000) Sodium butyrate-induced differentiation of human LIM2537 colon cancer cells decreases GSK-3β activity and increases levels of both membrane-bound and Apc/axin/GSK-3β complex-associated pools of β-catenin. Oncol. Res. 12, 193-201. <https://doi.org/10.3727/096504001108747684>
109. Warrell, R. P., Jr., He, L. Z., Richon, V., Calleja, E., Pandolfi, P. P. (1998) Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. J. Natl. Cancer Inst. 90, 1621-1625. <https://doi.org/10.1093/jnci/90.21.1621>
110. Werling, U., Siehler, S., Litfin, M., Nau, H., Gottlicher, M. (2001) Induction of differentiation in F9 cells and activation of peroxisome proliferator-activated receptor δ by valproic acid and its teratogenic derivatives. Mol. Pharmacol. 59, 1269-1276. <https://doi.org/10.1016/S0026-895X(24)12588-6>
111. Williams, R. S., Cheng, L., Mudge, A. W., Harwood, A. J. (2002) A common mechanism of action for three mood- stabilizing drugs. Nature 417, 292-295. <https://doi.org/10.1038/417292a>
112. Wong, H., Kumar, S., Rurak, D. W., Kwan, E., Abbott, F. S., Riggs, K. W. (2000) Ontogeny of valproic acid disposition and metabolism: a developmental study in postnatal lambs and adult sheep. Drug Metab. Dispos. 28, 912-919. <https://doi.org/10.1016/S0090-9556(24)15163-X>
113. Xia, Q., Sung, J., Chowdhury, W., Chen, C. L., Hoti, N., Shabbeer, S., Carducci, M., Rodriguez, R. (2006) Chronic administration of valproic acid inhibits prostate cancer cell growth in vitro and in vivo. Cancer Res. 66, 7237-7244. <https://doi.org/10.1158/0008-5472.CAN-05-0487>
114. Yamamoto-Yamaguchi, Y., Okabe-Kado, J., Kasukabe, T., Honma, Y. (2003) Induction of apoptosis by combined treatment with differentiation-inducing agents and interferon-α in human lung cancer cells. Anticancer Res. 23, 2537-2547.
115. Yoo, C. B., Jones, P. A. (2006) Epigenetic therapy of cancer: past, present and future. Nat. Rev. Drug Discov. 5, 37-50. <https://doi.org/10.1038/nrd1930>
116. Yuan, P. X., Huang, L. D., Jiang, Y. M., Gutkind, J. S., Manji, H. K., Chen, G. (2001) The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth. J. Biol. Chem. 276, 31674-31683. <https://doi.org/10.1074/jbc.M104309200>
117. Zgouras, D., Becker, U., Loitsch, S., Stein, J. (2004) Modulation of angiogenesis-related protein synthesis by valproic acid. Biochem. Biophys. Res. Commun. 316, 693-697. <https://doi.org/10.1016/j.bbrc.2004.02.105>
front cover

ISSN 0015-5500 (Print) ISSN 2533-7602 (Online)

Open access journal

Submissions

Archive