title: Molecular changes induced by the curcumin analogue D6 in human melanoma cells.
abstract: BACKGROUND
  In a previous report, we described the in vitro and in vivo antiproliferative and proapoptotic activity of a hydroxylated biphenyl (D6), a structural analogue of curcumin, on malignant melanoma and neuroblastoma tumours. In this paper, we investigated the molecular changes induced by such a compound, underlying cell growth arrest and apoptosis in melanoma cells.
  
  
  RESULTS
  To shed light on the mechanisms of action of D6, we firstly demonstrated its quick cellular uptake and subsequent block of cell cycle in G2/M phase transition. A gene expression profile analysis of D6-treated melanoma cells and fibroblasts was then carried out on high density microarrays, to assess gene expression changes induced by this compound. The expression profile study evidenced both an induction of stress response pathways and a modulation of cell growth regulation mechanisms. In particular, our data suggest that the antiproliferative and proapoptotic activities of D6 in melanoma could be partially driven by up-regulation of the p53 signalling pathways as well as by down-regulation of the PI3K/Akt and NF-kB pathways. Modulation of gene expression due to D6 treatment was verified by western blot analysis for single proteins of interest, confirming the results from the gene expression profile analysis.
  
  
  CONCLUSIONS
  Our findings contribute to the understanding of the mechanisms of action of D6, through a comprehensive description of the molecular changes induced by this compound at the gene expression level, in agreement with the previously reported anti-tumour effects on melanoma cells.
authors: Biomolecular Chemistry Institute, National Research Council of Italy, Traversa La Crucca, 3. 07100, Sassari, Italy. carla.rozzo@icb.cnr.it
authors: Carla
authors: C
authors: Rozzo
authors: Manuela
authors: M
authors: Fanciulli
authors: Cristina
authors: C
authors: Fraumene
authors: Antonio
authors: A
authors: Corrias
authors: Tiziana
authors: T
authors: Cubeddu
authors: Ilaria
authors: I
authors: Sassu
authors: Sara
authors: S
authors: Cossu
authors: Valentina
authors: V
authors: Nieddu
authors: Grazia
authors: G
authors: Galleri
authors: Emanuela
authors: E
authors: Azara
authors: Maria Antonietta
authors: MA
authors: Dettori
authors: Davide
authors: D
authors: Fabbri
authors: Giuseppe
authors: G
authors: Palmieri
authors: Marina
authors: M
authors: Pisano
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013312:Stress, Physiological / Q000187:drug effects; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin
references: J Transl Med. 2012 Jul 04;10:83
references: 22551296
references: Clin Dermatol. 2010 Nov-Dec;28(6):644-9
references: 21034988
references: Mol Cancer. 2007 Jan 18;6:8
references: 17233906
references: Nature. 1999 Sep 2;401(6748):82-5
references: 10485710
references: Carcinogenesis. 2004 Nov;25(11):2155-64
references: 15271854
references: Cell Death Differ. 2004 Apr;11(4):381-9
references: 14685163
references: Nat Rev Clin Oncol. 2011 May 24;8(7):426-33
references: 21606968
references: Nat Methods. 2012 Jul;9(7):671-5
references: 22930834
references: Nat Prod Rep. 2011 Nov;28(12):1937-55
references: 21979811
references: Proc Natl Acad Sci U S A. 1990 Mar;87(5):1663-7
references: 1689846
references: Pigment Cell Res. 2007 Dec;20(6):466-84
references: 17935490
references: Cancer Lett. 2008 Aug 18;267(1):133-64
references: 18462866
references: Mol Cancer Ther. 2009 Sep;8(9):2726-35
references: 19723881
references: J Biol Chem. 1999 Apr 9;274(15):10287-92
references: 10187815
references: Melanoma Res. 2005 Aug;15(4):235-44
references: 16034300
references: Nat Rev Mol Cell Biol. 2004 Sep;5(9):739-51
references: 15340381
references: N Engl J Med. 2010 Aug 19;363(8):711-23
references: 20525992
references: Adv Exp Med Biol. 2007;595:173-84
references: 17569210
references: Curr Mol Med. 2012 Jun;12(5):634-51
references: 22515981
references: Cell. 2000 Dec 8;103(6):839-42
references: 11136969
references: Mol Cell Biochem. 2010 Mar;336(1-2):85-95
references: 19826768
references: J Cell Sci. 2002 Jul 15;115(Pt 14):2809-16
references: 12082142
references: Cancer. 2005 Aug 15;104(4):879-90
references: 16007726
references: Cancer Lett. 2008 Oct 8;269(2):199-225
references: 18479807
references: Mol Cancer. 2010 Jun 03;9:137
references: 20525240
references: J Clin Oncol. 2006 Sep 10;24(26):4340-6
references: 16908931
references: Int J Biochem Cell Biol. 1999 Oct;31(10):1037-51
references: 10582338
references: Melanoma Res. 2004 Jun;14(3):165-71
references: 15179184
references: Mol Cell Biol. 1999 May;19(5):3485-95
references: 10207072
references: Cell. 2007 Aug 24;130(4):597-600
references: 17719538
references: Proc Natl Acad Sci U S A. 2004 May 11;101(19):7386-91
references: 15123817
references: Br J Cancer. 2007 Jan 29;96(2):196-200
references: 17211478
references: Cancer J. 2012 Mar-Apr;18(2):142-7
references: 22453015
references: N Engl J Med. 2011 Jun 30;364(26):2507-16
references: 21639808
references: Science. 2000 May 12;288(5468):1053-8
references: 10807576
references: Oncogene. 2003 May 19;22(20):3076-80
references: 12789283
references: J Transl Med. 2009 Oct 14;7:86
references: 19828018
references: Nat Rev Drug Discov. 2009 Jan;8(1):33-40
references: 19116625
references: Cell Prolif. 2003 Jun;36(3):131-49
references: 12814430
references: Genes Dev. 2006 Aug 15;20(16):2149-82
references: 16912270
references: Nature. 2010 Jul 1;466(7302):138-42
references: 20596027
references: Cell Signal. 2011 Jul;23(7):1076-81
references: 21144894
references: Biochim Biophys Acta. 2008 Apr;1780(4):673-9
references: 18178166
references: Biochim Biophys Acta. 2006 Oct;1760(10):1513-20
references: 16904830
references: Oncology (Williston Park). 2009 May;23(6):488-96
references: 19544689
references: Cell. 1996 Jul 26;86(2):263-74
references: 8706131
references: Bioinformatics. 2003 Dec 12;19(18):2448-55
references: 14668230
references: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references: 20610543
references: J Biol Chem. 2011 Dec 9;286(49):42232-42247
references: 22013068
references: Int J Oncol. 2000 May;16(5):871-86
references: 10762622
references: Cancer Ther. 2009;7(A):268-276
references: 19652693
references: Int J Cancer. 2004 Sep 10;111(4):575-83
references: 15239136
references: Nutr Cancer. 2011;63(2):161-73
references: 21294053
references: Cell Stress Chaperones. 2007 Autumn;12(3):219-29
references: 17915554
references: Apoptosis. 2002 Aug;7(4):335-45
references: 12101393
references: Dermatol Clin. 2009 Apr;27(2):205-14, viii
references: 19254665
references: Nat Rev Cancer. 2009 Jun;9(6):400-14
references: 19440234