Metabolic approach to the enhancement of antitumor effect of chemotherapy: A key role of acetyl-L-carnitine

Clinical Cancer Research

Volumn 16, Issue 15, 2010, Pages 3944-3953

  Pisano, Claudio ^a   Vesci, Loredana ^a   Milazzo, Ferdinando Maria ^a   Guglielmi, Mario Berardino ^a   Foderà, Rosanna ^a   Barbarino, Marcella ^a   D'Incalci, Maurizio ^b   Zucchetti, Massimo ^b   Petrangolini, Giovanna ^c   Tortoreto, Monica ^c   Perego, Paola ^c   Zuco, Valentina ^c   Orlandi, Augusto ^d   Passeri, Daniela ^d   Carminati, Paolo ^a   Cavazza, Claudio ^a   Zunino, Franco ^c  

^a Sigma Tau SpA   (Italy)

^b MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^c NATIONAL CANCER INSTITUTE   (Italy)

^d UNIVERSITY OF ROME TOR VERGATA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCARNITINE; CARBOPLATIN; CISPLATIN; HISTONE DEACETYLASE INHIBITOR; PROTEIN P53; ST 3595; UNCLASSIFIED DRUG;

ACETYLATION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CHEMOTHERAPY; CELL PROLIFERATION; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENTIATION; DRUG SENSITIVITY; FEMALE; GENE TARGETING; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; LUNG METASTASIS; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ACETYLCARNITINE; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; BLOTTING, WESTERN; CARBOPLATIN; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CISPLATIN; FEMALE; HISTONE DEACETYLASE INHIBITORS; HUMANS; IN SITU NICK-END LABELING; LUNG NEOPLASMS; MALE; MICE; MICE, NUDE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; TUMOR SUPPRESSOR PROTEIN P53; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77955102628     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-10-0964     Document Type: Article

References (33)

1. Bremer J. Carnitine metabolism and functions. Physiol Rev 1983;63:1420-80.
2. Bieber LL. Carnitine. Annu Rev Biochem 1988;57:261-83.
3. Steiber A, Kerner J, Hoppel CL. Carnitine: a nutritional, biosynthetic, and functional perspective. Mol Aspects Med 2004;25:455-73.
4. Calabrese V, Giuffrida Stella AM, Calvani M, Butterfield DA. Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes. J Nutr Biochem 2006;17:73-88. (Pubitemid 43082141)
5. Pisano C, Pratesi G, Laccabue D, et al. Paclitaxel and cisplatin-induced neurotoxicity: a protective role of acetyl-L-carnitine. Clin Cancer Res 2003;9:5756-67.
6. Madiraju P, Pande SV, Prentki M, Murthy Madiraju SR. Mitochondrial acetylcarnitine provides acetyl groups for nuclear histone. Epigenetics 2009;4:399-403.
7. Lavin MF, Gueven N. The complexity of p53 stabilization and activation. Cell Death Differ 2006;13:941-50.
8. Glozak MA, Sengupta N, Zhang X, Seto E. Acetylation and deacetylation of non-histone proteins. Gene 2005;363:15-23.
9. Lu C, El-Deiry WS. Targeting p53 for enhanced radio- and chemosensitivity. Apoptosis 2009;14:597-606.
10. Beretta GL, Gatti L, Benedetti V, Perego P, Zunino F. Small molecules targeting p53 to improve antitumor therapy. Mini Rev Med Chem 2008;8:856-68.
11. Righetti SC, Della Torre G, Pilotti S, et al. A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res 1996;56:689-93.
12. Shelling AN. Role of p53 in drug resistance in ovarian cancer. Lancet 1997;349:744-5.
13. Perego P, Romanelli S, Carenini N, et al. Ovarian cancer cisplatin-resistant cell lines: multiple changes including collateral sensitivity to taxol. Ann Oncol 1998;9:423-30.
14. Workman P, Twentyman P, Balkwill F, et al. United Kingdom Coordinating Committee on Cancer Research (UKCCCR) guidelines for the welfare of animals in experimental neoplasia (second edition). Br J Cancer 1998;77:1-10.
15. Cassinelli G, Lanzi C, Petrangolini G, et al. Inhibition of c-Met and prevention of spontaneous metastatic spreading by the 2-indolinone RPI-1. Mol Cancer Ther 2006;5:2388-97.
16. Gatti L, Supino R, Perego P, et al. Apoptosis and growth arrest induced by platinum compounds in U2-OS cells reflect a specific DNA damage recognition associated with a different p53-mediated response. Cell Death Differ 2002;9:1352-9.
17. Valenzuela-Fernandez A, Cabrero JR, Serrador JM, Sanchez-Madrid F. HDAC6: a key regulator of cytoskeleton, cell migration and cell-cell interactions. Cell 2008;18:291-7.
18. Kapoor S. Inhibition of HDAC6-dependent carcinogenesis: emerging, new therapeutic options besides belinostat. Int J Cancer 2009;124:509.
19. Dallavalle S, Cincinelli R, Nannei R, et al. Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. Eur J Med Chem 2009;44:1900-12.
20. Hockenberry MJ, Hooke MC, Gregurich M, McCarthy K. Carnitine plasma levels and fatigue in children/adolescents receiving cisplatin, ifosfamide, or doxorubicin. J Pediatr Hematol Oncol 2009;31:664-9.
21. Haschke M, Vitins T, Lüde S, et al. Urinary excretion of carnitine as a marker of proximal tubular damage associated with platin-based antineoplastic drugs. Nephrol Dial Transplant 2010;25:426-33.
22. Munshi A, Kurland JF, Nishikawa T, et al. Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity. Clin Cancer Res 2005;11:4912-22. (Pubitemid 41557212)
23. Munshi A, Tanaka T, Hobbs ML, Tucker SL, Richon VM, Meyn RE. Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of γ-H2AX foci. Mol Cancer Ther 2006;5:1967-74.
24. Kim IA, Shin JH, Kim JH, et al. Histone deacetylase inhibitor-mediated radiosensitization of human cancer cells: class differences and the potential influence of p53. Clin Cancer Res 2006;12:940-9.
25. Chen C-S, Wang Y-C, Yang H-C, et al. Histone deacetylase inhibitors sensitize prostate cancer cells to agents that produce DNA double-strand breaks by targeting Ku70 acetylation. Cancer Res 2007;67:5318-27.
26. Ozaki K, Kishikawa F, Tanaka M, Sakamoto T, Tanimura S, Kohno M. Histone deacetylase enhance the chemosensitivity of tumor cells with cross-resistance to a wide range of DNA-damaging drugs. Cancer Sci 2008;99:376-84.
27. Geng L, Cuneo KC, Fu A, et al. Histone deacetylase (HDAC) inhibitor LBH589 increases duration of γ-H2AX foci and confines HDAC4 ti cytoplasm in irradiated non-small cell lung cancer. Cancer Res 2006;66:11298-304.
28. Kim E, Giese A, Deppert W. Wild-type p53 in cancer cells: when a guardian turns into a blackguard. Biochem Pharmacol 2009;77:11-20.
29. Vekris A, Meynard D, Haaz MC, Bayssas M, Bonneti J, Robert J. Molecular determinants of the cytotoxicity of platinum compounds: the contribution of in silico research. Cancer Res 2004;64:356-62.
30. Tang Y, Zhao W, Chen Y, Zhao Y, Gu W. Acetylation is indispensable for p53 activation. Cell 2008;133:612-26.
31. Wallace DC, Fan W. Energetics, epigenetics, mitochondrial genetics. Mitochondrion 2010;10:12-31.
32. Tufekci O, Gunes D, Ozugul C, et al. Evaluation of the effect of acetyl-L-carnitine on experimental cisplatin nephrotoxicity. Chemotherapy 2009;55:451-9.
33. Bianchi G, Vitali G, Caraceni A, et al. Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine. Eur J Cancer 2005;41:1746-50.