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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2014

Open Access 01-12-2014 | Research

CELLFOOD™ induces apoptosis in human mesothelioma and colorectal cancer cells by modulating p53, c-myc and pAkt signaling pathways

Authors: Barbara Nuvoli, Raffaela Santoro, Simona Catalani, Serafina Battistelli, Serena Benedetti, Franco Canestrari, Rossella Galati

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2014

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Abstract

Background

CELLFOOD™ (CF) is a nutraceutical non-addictive, non-invasive, and completely non-toxic unique proprietary colloidal-ionic formula. Little is known about its effect on cancer cells in solid tumors. The aim of this study was to evaluate the effect that CF has on different cancer cell lines and the mechanism by which the nutraceutical works.

Methods

The effect of CF on HFF (normal fibroblasts), Met5A (mesothelium), MSTO-211H, NCI-2452, Ist-Mes1, MPP89, Ist-Mes2 (mesothelioma), M14 (melanoma), H1650, H1975 (lung cancer), SKRB3 (breast cancer), and HCT-116 (colorectal cancer) cell growth was tested by cell proliferation and clonogenic assay. Among all of them, MSTO-211 and HCT-116 were analyzed for cell cycle by flow cytometry and western blot.

Results

All human cancer lines were suppressed on cell growth upon 1:200 CF treatment for 24 and 48 hours. Death was not observed in HFF and Met5A cell lines. Cell cycle analysis showed an increased sub-G1 with reduction of G1 in MSTO-211 and a cell cycle arrest of in G1 in HCT116. Activation of caspase-3 and cleavage of PARP confirmed an apoptotic death for both cell lines. Increased expression levels of p53, p21, and p27, downregulation of c-myc and Bcl-2, and inhibition of Akt activation were also found in CF-treated MSTO-211 and HCT-116 cells.

Conclusions

These findings ascertained an interaction between p53, c-myc, p21, p27, Bcl-2, PI3K/Akt pathway, and CF-induced apoptosis in MSTO-211H and HCT-116 cells, suggesting that CF acts as an important regulator of cell growth in human cancer cell lines. CF could be a useful nutraceutical intervention for prevention in colon cancer and mesothelioma.
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Literature
1.
Benedetti S, Catalani S, Palma F, Canestrari F: The antioxidant protection of CELLFOOD against oxidative damage in vitro. Food Chem Toxicol. 2011, 49: 2292-2298. 10.1016/j.fct.2011.06.029.CrossRefPubMed
2.
Nieddu ME, Menza L, Baldi F, Frediani B, Marcolongo R: Efficacy of Cellfood’s therapy (deutrosulfazyme) in fibromyalgia. Reumatismo. 2007, 59: 316-321.PubMed
3.
Catalani S, Carbonaro V, Palma F, Arshakyan M, Galati R, Nuvoli B, Battistelli S, Canestrari F, Benedetti S: Metabolism modifications and apoptosis induction after CellfoodTM administration to leukemia cell lines. J Exp Clin Cancer Res. 2013, 32: 63-10.1186/1756-9966-32-63.PubMedCentralCrossRefPubMed
4.
Green DR, Evan GI: A matter of life and death. Cancer Cell. 2002, 1: 19-30. 10.1016/S1535-6108(02)00024-7.CrossRefPubMed
5.
Datta SR, Brunet A, Greenberg ME: Cellular survival: a play in three Akts. Genes Dev. 1999, 13: 2905-2927. 10.1101/gad.13.22.2905.CrossRefPubMed
6.
Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW: Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991, 51: 6304-6311.PubMed
7.
Mansur CP: The regulation and function of the p53 tumor suppressor. Adv Dermatol. 1997, 13: 121-166.PubMed
8.
Sandor J, Ambrus T, Ember I: The function of the p53 gene suppressor in carcinogenesis. Orv Hetil. 1995, 136: 1875-1883.PubMed
9.
Schoneich C: Protein modification in aging: an update. Exp Gerontol. 2006, 41: 807-812. 10.1016/j.exger.2006.07.002.CrossRefPubMed
10.
11.
Gottlieb TM, Oren M: p53 in growth control and neoplasia. Biochim Biophys Acta. 1996, 1287: 77-102.PubMed
12.
Levy N, Yonish-Rouach E, Oren M, Kimchi A: Complementation by wild-type p53 of interleukin-6 effects on M1 cells: induction of cell cycle exit and cooperativity with c-myc suppression. Mol Cell Biol. 1993, 13: 7942-7952.PubMedCentralCrossRefPubMed
13.
Vennstrom B, Sheiness D, Zabielski J, Bishop JM: Isolation and characterization of c-myc, a cellular homolog of the oncogene (v-myc) of avian myelocytomatosis virus strain 29. J Virol. 1982, 42: 773-779.PubMedCentralPubMed
14.
Pelengaris S, Khan M, Evan G: c-MYC: more than just a matter of life and death. Nat Rev Cancer. 2002, 2: 764-776. 10.1038/nrc904.CrossRefPubMed
15.
Vita M, Henriksson M: The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol. 2006, 16: 318-330. 10.1016/j.semcancer.2006.07.015.CrossRefPubMed
16.
Meyer N, Penn LZ: Reflecting on 25 years with MYC. Nat Rev Cancer. 2008, 8: 976-990. 10.1038/nrc2231.CrossRefPubMed
17.
Amati B, Alevizopoulos K, Vlach J: Myc and the cell cycle. Front Biosci. 1998, 3: D250-D268.PubMed
18.
19.
Eilers M: Control of cell proliferation by Myc family genes. Mol Cells. 1999, 9: 1-6.PubMed
20.
21.
Gartel AL, Ye X, Goufman E, Shianov P, Hay N, Najmabadi F, Tyner AL: Myc represses the p21(WAF1/CIP1) promoter and interacts with Sp1/Sp3. Proc Natl Acad Sci U S A. 2001, 98: 4510-4515. 10.1073/pnas.081074898.PubMedCentralCrossRefPubMed
22.
Müller D, Bouchard C, Rudolph B, Steiner P, Stuckmann I, Saffrich R, Ansorge W, Huttner W, Eilers M: Cdk2-dependent phosphorylation of p27 facilitates its Myc-induced release from cyclin E/cdk2 complexes. Oncogene. 1997, 15: 2561-2576. 10.1038/sj.onc.1201440.CrossRefPubMed
23.
Sherr CJ, Roberts JM: CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999, 13: 1501-1512. 10.1101/gad.13.12.1501.CrossRefPubMed
24.
Strasser A, Harris AW, Bath ML, Cory S: Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature. 1990, 348: 331-333. 10.1038/348331a0.CrossRefPubMed
25.
Del Poeta G, Venditti A, Del Principe MI, Maurillo L, Buccisano F, Tamburini A, Cox MC, Franchi A, Bruno A, Mazzone C, Panetta P, Suppo G, Masi M, Amadori S: Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood. 2003, 101: 2125-2131. 10.1182/blood-2002-06-1714.CrossRefPubMed
26.
Minn AJ, Rudin CM, Boise LH, Thompson CB: Expression of bcl-xL can confer a multidrug resistance phenotype. Blood. 1995, 86: 1903-1910.PubMed
27.
Yoshino T, Shiina H, Urakami S, Kikuno N, Yoneda T, Shigeno K, Igawa M: Bcl-2 expression as a predictive marker of hormone-refractory prostate cancer treated with taxane-based chemotherapy. Clin Cancer Res. 2006, 12: 6116-6124. 10.1158/1078-0432.CCR-06-0147.CrossRefPubMed
28.
Li ZX, Ouyang KQ, Jiang X, Wang D, Hu Y: Curcumin induces apoptosis and inhibits growth of human Burkitt’s lymphoma in xenograft mouse model. Mol Cells. 2009, 27: 283-289. 10.1007/s10059-009-0036-9.CrossRefPubMed
29.
Leow PC, Tian Q, Ong ZY, Yang Z, Ee PL: Antitumor activity of natural compounds, curcumin and PKF118–310, as Wnt/beta-catenin antagonists against human osteosarcoma cells. Invest New Drugs. 2010, 28: 766-782. 10.1007/s10637-009-9311-z.CrossRefPubMed
30.
Kunnumakkara AB, Diagaradjane P, Guha S, Deorukhkar A, Shentu S, Aggarwal BB, Krishnan S: Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factorkappaB- regulated gene products. Clin Cancer Res. 2008, 14: 2128-2136. 10.1158/1078-0432.CCR-07-4722.CrossRefPubMed
31.
Hong WK, Sporn MB: Recent advances in chemoprevention of cancer. Science. 1997, 278: 1073-1077. 10.1126/science.278.5340.1073.CrossRefPubMed
32.
Wattenberg LW: What are the critical attributes for cancer chemopreventive agents?. Ann NY Acad Sci. 1995, 768: 73-81. 10.1111/j.1749-6632.1995.tb12111.x.CrossRefPubMed
33.
Smith TJ, Hong J-Y, Wang Z-Y, Yang CS: How can carcinogenesis be inhibited?. Ann NY Acad Sci. 1995, 768: 82-90. 10.1111/j.1749-6632.1995.tb12112.x.CrossRefPubMed
34.
Sun SY, Hail N, Lotan R: Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst. 2004, 96: 662-672. 10.1093/jnci/djh123.CrossRefPubMed
35.
Huang Y, Hu J, Zheng J, Li J, Wei T, Zheng Z, Chen Y: Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in CA46 Burkitt lymphoma cells by baicalin. J Exp Clin Cancer Res. 2012, 31: 48-10.1186/1756-9966-31-48.PubMedCentralCrossRefPubMed
36.
Krifa M, Alhosin M, Muller CD, Gies JP, Chekir-Ghedira L, Ghedira K, Mély Y, Bronner C, Mousli M: Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16 INK4A re-expression related to UHRF1 and DNMT1 down-regulation. J Exp Clin Cancer Res. 2013, 32: 30-10.1186/1756-9966-32-30.PubMedCentralCrossRefPubMed
37.
38.
Warburg O: On respiratory impairment in cancer cells. Science. 1956, 124: 269-270.PubMed
39.
Shannon AM, Bouchier-Hayes DJ, Condron CM, Toomey D: Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev. 2003, 29: 297-307. 10.1016/S0305-7372(03)00003-3.CrossRefPubMed
40.
Harris AL: Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer. 2002, 2: 38-47. 10.1038/nrc704.CrossRefPubMed
41.
Iorio EL: Hypoxia, free radicals and antioxidants. The “Deutrosulfazyme®” paradox. Hypoxia Med J. 2006, 1: 2-32.
42.
Ferrero E, Fulgenzi A, Belloni D, Foglieni C, Ferrero ME: Cellfood™ improves respiratory metabolism of endothelial cells and inhibits hypoxia-induced reactive oxygen species (ROS) generation. J Physiol Pharmacol. 2011, 62: 287-293.PubMed
43.
Robinson LA, Reilly RB: Localized pleural mesothelioma. The clinical spectrum. Chest. 1994, 106: 1611-1615. 10.1378/chest.106.5.1611.CrossRefPubMed
44.
Broaddus VC: Asbestos, the mesothelial cell and malignancy: a matter of life or death. Am J Respir Cell Mol Biol. 1997, 17: 657-659. 10.1165/ajrcmb.17.6.f141.CrossRefPubMed
45.
World Health Organization: Cancer Incidence in Five Continents. 2002, Lyon: The World Health Organization and The International Agency for Research on Cancer
46.
Starzynska T, Bromley M, Ghosh A, Stern PL: Prognostic significance of p53 overexpression in gastric and colorectal carcinoma. Br J Cancer. 1992, 66: 558-562. 10.1038/bjc.1992.314.PubMedCentralCrossRefPubMed
47.
Altomare DA, Menges CW, Xu J, Pei J, Zhang L, Tadevosyan A, Neumann-Domer E, Liu Z, Carbone M, Chudoba I, Klein-Szanto AJ, Testa JR: Losses of both products of the Cdkn2a/Arf locus contribute to asbestos-induced mesothelioma development and cooperate to accelerate tumorigenesis. PLoS ONE. 2011, 6 (4): e18828-10.1371/journal.pone.0018828.PubMedCentralCrossRefPubMed
48.
Boxer LM, Dang CV: Translocations involving c-myc and c-myc function. Oncogene. 2001, 20: 5595-5610. 10.1038/sj.onc.1204595.CrossRefPubMed
49.
Adhikary S, Eilers M: Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol. 2005, 6: 635-645. 10.1038/nrm1703.CrossRefPubMed
50.
Ramael M, Van den Bossche J, Buysse C, Deblier I, Segers K, Van Marck E: Immunoreactivity for c-fos and c-myc protein with the monoclonal antibodies 14E10 and 6E10 in malignant mesothelioma and non-neoplastic mesothelium of the pleura. Histol Histopathol. 1995, 10: 639-643.PubMed
51.
Smith DR, Goh HS: Overexpression of the c-myc proto-oncogene in colorectal carcinoma is associated with a reduced mortality that is abrogated by point mutation of the p53 tumor suppressor gene. Clin Cancer Res. 1996, 2: 1049-1053.PubMed
52.
Marshall GM, Gherardi S, Xu N, Neiron Z, Trahair T, Scarlett CJ, Chang DK, Liu PY, Jankowski K, Iraci N, Haber M, Norris MD, Keating J, Sekyere E, Jonquieres G, Stossi F, Katzenellenbogen BS, Biankin AV, Perini G, Liu T: Transcriptional upregulation of histone deacetylase 2 promotes Myc-induced oncogenic effects. Oncogene. 2010, 29: 5957-5968. 10.1038/onc.2010.332.CrossRefPubMed
53.
Adams JM, Harris AW, Pinkert CA, Corcoran LM, Alexander WS, Cory S, Palmiter RD, Brinster RL: The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985, 318: 533-538. 10.1038/318533a0.CrossRefPubMed
54.
Morgenbesser SD, DePinho RA: Use of transgenic mice to study myc family gene function in normal mammalian development and in cancer. Semin Cancer Biol. 1994, 5: 21-36.PubMed
55.
Nasi S, Ciarapica R, Jucker R, Rosati J, Soucek L: Making decisions through Myc. FEBS Lett. 2001, 490: 153-162. 10.1016/S0014-5793(01)02118-4.CrossRefPubMed
56.
Oka N, Tanimoto S, Taue R, Nakatsuji H, Kishimoto T, Izaki H, Fukumori T, Takahashi M, Nishitani M, Kanayama HO: Role of phosphatidylinositol-3 kinase/Akt pathway in bladder cancer cell apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand. Cancer Sci. 2006, 97: 1093-1098. 10.1111/j.1349-7006.2006.00294.x.CrossRefPubMed
57.
Dieterle A, Orth R, Daubrawa M, Grotemeier A, Alers S, Ullrich S, Lammers R, Wesselborg S, Stork B: The Akt inhibitor triciribine sensitizes prostate carcinoma cells to TRAIL-induced apoptosis. Int J Cancer. 2009, 125: 932-941. 10.1002/ijc.24374.CrossRefPubMed
58.
Oki E, Baba H, Tokunaga E, Nakamura T, Ueda N, Futatsugi M, Mashino K, Yamamoto M, Ikebe M, Kakeji Y, Maehara Y: Akt phosphorylation associates with LOH of PTEN and leads to chemoresistance for gastric cancer. Int J Cancer. 2005, 117: 376-380. 10.1002/ijc.21170.CrossRefPubMed
59.
Kai K, D'Costa S, Sills RC, Kim J: Inhibition of the insulin-like growth factor 1 receptor pathway enhances the antitumor effect of cisplatin in human malignant mesothelioma cell lines. Cancer Lett. 2009, 278: 49-55. 10.1016/j.canlet.2008.12.023.CrossRefPubMed
60.
Opitz I, Soltermann A, Abaecherli M, Hinterberger M, Probst-Hensch N, Stahel R, Moch H, Weder W: PTEN expression is a strong predictor of survival in mesothelioma patients. Eur J Cardiothorac Surg. 2008, 33: 502-506. 10.1016/j.ejcts.2007.09.045.CrossRefPubMed
61.
Pugazhenthi S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE, Reusch JE: Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem. 2000, 275: 10761-10766. 10.1074/jbc.275.15.10761.CrossRefPubMed
62.
Manion MK, Hockenbery DM: Targeting BCL-2- related proteins in cancer therapy. Cancer Biol Ther. 2003, 2: S105-S114.CrossRefPubMed
63.
Li L, Haynes P, Bender JR: Plasma membrane localization and function of the estrogen receptor α variant (ER46) in human endothelial cells. Proc Natl Acad Sci U S A. 2003, 100: 4807-4812. 10.1073/pnas.0831079100.PubMedCentralCrossRefPubMed
Metadata
Title
CELLFOOD™ induces apoptosis in human mesothelioma and colorectal cancer cells by modulating p53, c-myc and pAkt signaling pathways
Authors
Barbara Nuvoli
Raffaela Santoro
Simona Catalani
Serafina Battistelli
Serena Benedetti
Franco Canestrari
Rossella Galati
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2014
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-33-24

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