Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2013

Open Access 01-12-2013 | Research

Molecular changes induced by the curcumin analogue D6 in human melanoma cells

Authors: Carla Rozzo, Manuela Fanciulli, Cristina Fraumene, Antonio Corrias, Tiziana Cubeddu, Ilaria Sassu, Sara Cossu, Valentina Nieddu, Grazia Galleri, Emanuela Azara, Maria Antonietta Dettori, Davide Fabbri, Giuseppe Palmieri, Marina Pisano

Published in: Molecular Cancer | Issue 1/2013

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
2.
Jemal A, Siegel R, Xu J, Ward E: Cancer statistics 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.CrossRefPubMed
3.
4.
Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, Dummer R, Garbe C, Testori A, Maio M, Hogg D, Lorigan P, Lebbe C, Jouary T, Schadendorf D, Ribas A, O'Day SJ, Sosman JA, Kirkwood JM, Eggermont AMM, Dreno B, Nolop K, Li J, Nelson B, Hou J, Lee RJ, Flaherty KT, McArthur GA, for the BRIM-3 Study Group: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011, 364: 2507-2516. 10.1056/NEJMoa1103782.PubMedCentralCrossRefPubMed
5.
Ribas A, Flaherty KT: BRAF targeted therapy changes the treatment paradigm in melanoma. Nat Rev Clin Oncol. 2011, 8: 426-433. 10.1038/nrclinonc.2011.69.CrossRefPubMed
6.
Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJM, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010, 363: 711-723. 10.1056/NEJMoa1003466.PubMedCentralCrossRefPubMed
7.
Ascierto PA, Grimaldi AM, Curti B, Faries MB, Ferrone S, Flaherty K, Fox BA, Gajewski TF, Gershenwald JE, Gogas H, Grossmann K, Hauschild A, Hodi FS, Kefford R, Kirkwood JM, Leachmann S, Maio M, Marais R, Palmieri G, Morton DL, Ribas A, Stroncek DF, Stewart R, Wang E, Mozzillo N, Marincola FM: Future perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge from Naples to the World. Napoli, December 5th-6th 2011". J. Transl Med. 2012, 10: 83-10.1186/1479-5876-10-83.PubMedCentralCrossRefPubMed
8.
Chin L, Garraway LA, Fisher DE: Malignant melanoma: genetics and therapeutics in the genomic era. Genes Dev. 2006, 20: 2149-2182. 10.1101/gad.1437206.CrossRefPubMed
9.
Palmieri G, Capone M, Ascierto ML, Gentilcore G, Stroncek DF, Casula M, Sini MC, Palla M, Mozzillo N, Ascierto PA: Main roads to melanoma. J Trans Med. 2009, 7: 86:1-86:17.CrossRef
10.
Shanmugam MK, Kannaiyan R, Sethi G: Targeting cell signaling and apoptotic pathways by dietary agents: role in the prevention and treatment of cancer. Nutr Cancer. 2011, 63: 161-173. 10.1080/01635581.2011.523502.CrossRefPubMed
11.
Jensen JD, Wing GJ, Dellavalle RP: Nutrition and melanoma prevention. Clin Dermatol. 2010, 28: 644-649. 10.1016/j.clindermatol.2010.03.026.CrossRefPubMed
12.
Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB: Curcumin and cancer: an "old-age" disease with an "age-old" solution. Cancer Lett. 2008, 267: 133-164. 10.1016/j.canlet.2008.03.025.CrossRefPubMed
13.
Kunwar A, Barik A, Mishra B, Rathinasamy K, Pandey R, Priyadarsini KI: Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells. Biochim Biophys Acta. 2008, 1780: 673-679. 10.1016/j.bbagen.2007.11.016.CrossRefPubMed
14.
Gupta SC, Prasad S, Kim JH, Patchva S, Webb LJ, Priyadarsini IK, Aggarwal BB: Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep. 2011, 28: 1937-1955. 10.1039/c1np00051a.PubMedCentralCrossRefPubMed
15.
Das T, Sa G, Saha B, Das K: Multifocal signal modulation therapy of cancer: ancient weapon, modern targets. Mol Cell Biochem. 2010, 336: 85-95. 10.1007/s11010-009-0269-0.CrossRefPubMed
16.
Kunnumakkara AB, Anand P, Aggarwal BB: Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett. 2008, 269: 199-225. 10.1016/j.canlet.2008.03.009.CrossRefPubMed
17.
Bill MA, Bakan C, Benson DM, Fuchs J, Young G, Lesinski GB: Curcumin induces proapoptotic effects against human melanoma cells and modulates the cellular response to immunotherapeutic cytokines. Mol Cancer Ther. 2009, 8: 2726-2735. 10.1158/1535-7163.MCT-09-0377.PubMedCentralCrossRefPubMed
18.
Lin CL, Lin JK: Curcumin: a potential cancer chemopreventive agent trough suppressing NF-kB signalling. J Cancer Mol. 2008, 4: 11-16.
19.
Zheng M, Ekmekcioglu S, Walch ET, Tang CH, Grimm EA: Inhibition of nuclear factor-kappaB and nitric oxide by curcumin induces G2/M cell cycle arrest and apoptosis in human melanoma cells. Melanoma Res. 2004, 14: 165-171. 10.1097/01.cmr.0000129374.76399.19.CrossRefPubMed
20.
Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R: Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer. 2005, 104: 879-890. 10.1002/cncr.21216.CrossRefPubMed
21.
Pisano M, Pagnan G, Dettori MA, Cossu S, Caffa I, Sassu I, Emionite L, Fabbri D, Cilli M, Pastorino F, Palmieri G, Delogu G, Ponzoni M, Rozzo C: Enhanced anti-tumor activity of a new curcumin-related compound against melanoma and neuroblastoma cells. Mol Cancer. 2010, 9: 137:1-137:12.CrossRef
22.
Carr KM, Bittner M, Trent JM: Gene-expression profiling in human cutaneous melanoma. Oncogene. 2003, 22: 3076-3080. 10.1038/sj.onc.1206448.CrossRefPubMed
23.
Hoek KS: DNA microarray analyses of melanoma gene expression: a decade in the mines. Pigment Cell Res. 2007, 20: 466-484. 10.1111/j.1600-0749.2007.00412.x.CrossRefPubMed
24.
Curtin JA, Busam K, Pinkel D, Bastian BC: Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006, 24: 4340-4346. 10.1200/JCO.2006.06.2984.CrossRefPubMed
25.
Oyadomari S, Mori M: Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 2004, 11: 381-389. 10.1038/sj.cdd.4401373.CrossRefPubMed
26.
Yan M, Lee J, Schilbach S, Goddard A, Dixit V: mE10, a novel caspase recruitment domain-containing proapoptotic molecule. J Biol Chem. 1999, 274: 10287-10292. 10.1074/jbc.274.15.10287.CrossRefPubMed
27.
McDonald ER, El-Deiry WS: Cell cycle control as a basis for cancer drug development. Int J Oncol. 2000, 16: 871-886.PubMed
28.
Nollen EA, Morimoto RI: Chaperoning signaling pathways: molecular chaperones as stress-sensing 'heat shock' proteins. J Cell Sci. 2002, 115: 2809-2816.PubMed
29.
Massé D, Ebstein F, Bougras G, Harb J, Meflah K, Grégoire M: Increased expression of inducible HSP70 in apoptotic cells is correlated with their efficacy for antitumor vaccine therapy. Int J Cancer. 2004, 111: 75-83.CrossRef
30.
Carta F, Demuro PP, Zanini C, Santona A, Castiglia D, D’Atri S, Ascierto PA, Napolitano M, Cossu A, Tadolini B, Turrini F, Manca A, Sini MC, Palmieri G, Rozzo C: Analysis of candidate genes through a proteomics-based approach in primary cell lines from malignant melanomas and their metastases. Melanoma Res. 2005, 15: 235-244. 10.1097/00008390-200508000-00002.CrossRefPubMed
31.
Oyadomari S, Araki E, Mori M: Endoplasmic reticulum stress mediated apoptosis in pancreatic beta-cells. Apoptosis. 2002, 7: 335-345. 10.1023/A:1016175429877.CrossRefPubMed
32.
33.
Scott DW, Loo G: Curcumin-induced GADD153 gene up-regulation in human colon cancer cells. Carcinogenesis. 2004, 25: 2155-2164. 10.1093/carcin/bgh239.CrossRefPubMed
34.
Erol A: Deciphering the intricate regulatory mechanisms for the cellular choice between cell repair, apoptosis or senescence in response to damaging signals. Cell Signal. 2011, 23: 1076-1081. 10.1016/j.cellsig.2010.11.023.CrossRefPubMed
35.
Aylon Y, Oren M: Living with p53, dying of p53. Cell. 2007, 130: 597-600. 10.1016/j.cell.2007.08.005.CrossRefPubMed
36.
37.
Cretu A, Sha X, Tront J, Hoffman B, Liebermann DA: Stress sensor Gadd45 genes as therapeutic targets in cancer. Cancer Ther. 2009, 7: 268-276.PubMedCentralPubMed
38.
Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N: Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 2000, 288: 1053-1058. 10.1126/science.288.5468.1053.CrossRefPubMed
39.
Vermeulen K, Van Bockstaele DR, Berneman ZN: The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 2003, 36: 131-149. 10.1046/j.1365-2184.2003.00266.x.CrossRefPubMed
40.
Tamura RE, de Vasconcellos JF, Sarkar D, Liebermann TA, Fisher PB, Zerbini LF: GADD45 proteins: central players in tumorigenesis. Curr. Mol. Med. 2012, 12: 634-651. 10.2174/156652412800619978.PubMedCentralCrossRefPubMed
41.
Huang DCS, Strasser A: BH3-Only Proteins - Essential Initiators of Apoptotic Cell Death. Cell. 2000, 103: 839-842. 10.1016/S0092-8674(00)00187-2.CrossRefPubMed
42.
43.
Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ: SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996, 86: 263-274. 10.1016/S0092-8674(00)80098-7.CrossRefPubMed
44.
Cardozo T, Pagano M: The SCF ubiquitin ligase: insights into a molecular machine. Nature Rev Mol Cell Biol. 2004, 5: 739-751.CrossRef
45.
D’Angiolella V, Donato V, Vijayakumar S, Saraf A, Florens L, Washburn MP, Dynlacht B, Pagano M: SCFCyclin F controls centrosome homeostasis and mitotic fidelity through CP110 degradation. Nature. 2010, 466: 138-142. 10.1038/nature09140.PubMedCentralCrossRefPubMed
46.
Ashman LK: The biology of stem cell factor and its receptor C-kit. Int J Biochem Cell Biol. 1999, 31: 1037-1051. 10.1016/S1357-2725(99)00076-X.CrossRefPubMed
47.
Davies MA: The role of the PI3K-AKT pathway in melanoma. Cancer J. 2012, 18: 142-147. 10.1097/PPO.0b013e31824d448c.CrossRefPubMed
48.
49.
Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB: NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase. Nature. 1999, 401: 82-85. 10.1038/43466.CrossRefPubMed
50.
Kuttan G, Kumar KB, Guruvayoorappan C, Kuttan R: Antitumor, anti-invasion, and antimetastatic effects of curcumin. Adv Exp Med Biol. 2007, 595: 173-184. 10.1007/978-0-387-46401-5_6.CrossRefPubMed
51.
Webster GA, Perkins ND: Transcriptional cross talk between NF-kappaB and p53. Mol Cell Biol. 1999, 19: 485-3495.CrossRef
52.
Iyer NG, Chin SF, Ozdag H, Daigo Y, Hu DE, Cariati M, Brindle K, Aparicio S, Caldas C: p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels. Proc Natl Acad Sci U S A. 2004, 101: 7386-7391. 10.1073/pnas.0401002101.PubMedCentralCrossRefPubMed
53.
Sen GS, Mohanty S, Hossain DM, Bhattacharyya S, Banerjee S, Chakraborty J, Saha S, Ray P, Bhattacharjee P, Mandal D, Bhattacharya A, Chattopadhyay S, Das T, Sa G: Curcumin enhances the efficacy of chemotherapy by tailoring p65NFkappaB-p300 cross-talk in favor of p53-p300 in breast cancer. J Biol Chem. 2011, 286: 42232-42247. 10.1074/jbc.M111.262295.PubMedCentralCrossRefPubMed
54.
Pisano M, Pagnan G, Loi M, Mura ME, Tilocca MG, Palmieri G, Fabbri D, Dettori MA, Delogu G, Ponzoni M, Rozzo C: Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells. Mol Cancer. 2007, 6: 8:1-8:1.CrossRef
55.
Kunwar A, Barik A, Pandey R, Priyadarsini KI: Transport of liposomal and albumin loaded curcumin to living cells: an absorption and fluorescence spectroscopic study. Biochim Biophys Acta. 2006, 1760: 1513-1520. 10.1016/j.bbagen.2006.06.012.CrossRefPubMed
56.
Van Gelder RN, von Zastrow ME, Yool A, Dement WC, Barchas JD, Eberwine JH: Amplified RNA synthesized from limited quantities of heterogeneous cDNA. Proc Natl Acad Sci U S A. 1990, 87: 1663-1667. 10.1073/pnas.87.5.1663.PubMedCentralCrossRefPubMed
57.
Wright GW, Simon RM: A random variance model for detection of differential gene expression in small microarray experiments. Bioinformatics. 2003, 19: 2448-2455. 10.1093/bioinformatics/btg345.CrossRefPubMed
58.
Schneider CA, Rasband WS, Eliceiri KW: NIH Image to ImageJ: 25 years of image analysis. Nat Met. 2012, 9: 671-675. 10.1038/nmeth.2089.CrossRef
Metadata
Title
Molecular changes induced by the curcumin analogue D6 in human melanoma cells
Authors
Carla Rozzo
Manuela Fanciulli
Cristina Fraumene
Antonio Corrias
Tiziana Cubeddu
Ilaria Sassu
Sara Cossu
Valentina Nieddu
Grazia Galleri
Emanuela Azara
Maria Antonietta Dettori
Davide Fabbri
Giuseppe Palmieri
Marina Pisano
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2013
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-12-37

Other articles of this Issue 1/2013

Molecular Cancer 1/2013 Go to the issue

Review

Epithelial-mesenchymal transition: focus on metastatic cascade, alternative splicing, non-coding RNAs and modulating compounds

Research

Correlation between centromere protein-F autoantibodies and cancer analyzed by enzyme-linked immunosorbent assay

Research

Combined p21-activated kinase and farnesyltransferase inhibitor treatment exhibits enhanced anti-proliferative activity on melanoma, colon and lung cancer cell lines

Short communication

Regulation of stem cell self-renewal and differentiation by Wnt and Notch are conserved throughout the adenoma-carcinoma sequence in the colon

Research

Expression analysis and in silico characterization of intronic long noncoding RNAs in renal cell carcinoma: emerging functional associations

Research

Growth factor receptor-Src-mediated suppression of GRK6 dysregulates CXCR4 signaling and promotes medulloblastoma migration
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits