K-D:rib dampens Hs 578T cancer cell chemoinvasion and proliferation

Cancer Cell International

Simonetta Croci²  Ida Ortalli²  Adesola A Babarinde¹  Luca Bruni² 

[1] Department of Chemical Sciences, Olabisi Onabanjo University, Ago-Iwoye, Ogun State, Nigeria;INBB National Institute of Biosystems and Biostructures, Rome, Italy

关键词: Doubling Population time;    D-ribose;    Potassium bicarbonate;    Chemotactic invasion assay;    Hs 578Bst (HTB-125) breast epithelial cell line;    Hs 578T (HTB-126) human breast cancer cell line;   

Others  :  1121675
DOI  :  10.1186/s12935-014-0077-9

 received in 2012-12-17, accepted in 2014-07-25,  发布年份 2014

【 摘 要 】

Background

Cancer cells, even in the presence of available oxygen, have a glycolysis enhancement. The “aerobic glycolysis” is known as the Warburg effect and it is considered one of the fundamental hallmarks of metabolic alteration during malignant transformation. A feature of many tumors is also a change into ions equilibrium, with particular reference to K⁺ intracellular concentration. Another hallmark in cancer is the reprogrammed chemotaxis pathways in favour of tumor cell dissemination.

Results

The doubling population time of 5 mM K:D-rib treated Hs 578T (HTB-126 ® ATCC) cell line is reduce by 30% respect to the control. During the chemotactic invasion assay, the relative number of motile and invasive cells, counted inside the FBS-AGAR spot, shows a decrease with the maintenance of the treatment reaching the 25% after nine days. Hs 578Bst (HTB-125 ® ATCC) non-tumor cell line treated for nineteen days with 5 mM K:D-rib was split twice as well as the control. No morphological change was visible in the treated respect to untreated cells.

Conclusions

We demonstrate that the synergic action of potassium bicarbonate and D-ribose has effect on Hs 578T cancer cell line proliferation reducing the cell cycle time. At 5 mM concentration, K:D-rib is able to modify the tumorigenic potential of human breast cancer cell line Hs 578T, interfering in vitro with the capability of Hs 578 T cell line to migrate under chemotactic stimuli. Despite this, K:D-rib solution, does not exhibit any appreciable toxicity as confirmed by the proliferation assay accomplished on Hs 578Bst cell line.

【 授权许可】

   
2014 Bruni et al.; licensee Springer

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Croci S, Pedrazzi G, Paoli G, Monetti D, Ortalli I: Potassium ascorbate as protective agent in the oxidation of the red blood cells. In Hyperfine Interactions (C), in proceedings of the International Conference on the application of Mössbauer Effect (ICAME 2001) 2–7 Semptember 2001 Oxford UK, Volume 5 Edited by Thomas MF, Williams JM, Gibb TC. 2001, 241-244.
• [2]Croci S, Pedrazzi G, Passeri G, Delsignore R, Ortalli I: Red cell Hb oxidation of healthy subjects compared to breast cancer patients. Anticancer Res 2002, 22(5):2903-2906.
• [3]Croci S, Pedrazzi G, Passeri G, Piccolo P, Ortalli I: Acetylphenylhydrazine induced haemoglobin oxidation in erythrocytes studied by Mossbauer spectroscopy. Biochim Biophys Acta 2001, 1568(1):99-104.
• [4]Boros LG, Lee PWN, Brandes JL, Cascante M, Muscarella P, Schirmer WJ, Melvin WS, Ellison EC: Nonoxidative pentose phosphate pathways and their direct role in ribose synthesis in tumors: is cancer a disease of cellular glucose metabolism? Med Hypotheses 1998, 50(1):55-59.
• [5]Freeman ML, Mertens-Talcott SU, St Cry J, Percival S: Ribose enhances retinoic acid-induced differentiation of HL-60 cells. Nutr Res 2008, 28(11):775-782.
• [6]Dai J, Carver M, Yang D: Polymorphism of human telomeric quadruplex structures. Biochimie 2008, 90(8):1172-1183.
• [7]Zhou XF, Su FY, Tian YQ, Youngbull C, Johnson RH, Meldrum DR: A new highly selective fluorescent K+ sensor. J Am Chem Soc 2011, 133(46):18530-18533.
• [8]Parkinson GN, Lee MPH, Neidle S: Crystal structure of parallel quadruplexes from human telomeric DNA. Nature 2002, 417(6891):876-880.
• [9]Lipps HJ, Rhodes D: G-quadruplex structures: in vivo evidence and function. Trends Cell Biol 2009, 19(8):414-422.
• [10]Kelland LR: Overcoming the immortality of tumor cells by telomere and telomerase based cancer therapeutics - current status and future prospects. Eur J Cancer 2005, 41(7):971-979.
• [11]Croci S, Bruni L, Bussolati S, Castaldo M, Dondi M: Potassium bicarbonate and D-ribose effects on A72 canine and HTB-126 human cancer cell line proliferation in vitro. Cancer Cell Int 2011, 11:30. BioMed Central Full Text
• [12]Anichini C, Lo Rizzo C, Longini M, Paoli G, Di Bartolo RM, Proietti F, Buonocore G: Beckwith-Wiedemann syndrome: potassium ascorbate with ribose therapy in a syndrome with high neoplastic risk. Anticancer Res 2011, 31(11):3973-3976.
• [13]Anichini C, Lotti F, Pietrini A, Lo Rizzo C, Longini M, Proietti F, Felici C, Buonocore G: Antioxidant effects of potassium ascorbate with ribose in costello syndrome. Anticancer Res 2013, 33(2):691-696.
• [14]Anichini C, Lotti F, Longini M, Proietti F, Felici C, Perrone S, Buonocore G: Antioxidant effects of potassium ascorbate with ribose therapy in a case with Prader Willi syndrome. Dis Markers 2012, 33(4):179-183.
• [15]Warburg O: Ueber den stoffwechsel der tumoren. Constable, London UK; 1930.
• [16]Pantziarka P: Li Fraumeni syndrome, cancer and senescence: a new hypothesis. Cancer Cell Int 2013, 13:35. BioMed Central Full Text
• [17]Heiden MGV, Cantley LC, Thompson CB: Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009, 324(5930):1029-1033.
• [18]Ferreira LMR: Cancer metabolism: the Warburg effect today. Exp Mol Pathol 2010, 89(3):372-380.
• [19]Hsu PP, Sabatini DM: Cancer cell metabolism: Warburg and beyond. Cell 2008, 134(5):703-707.
• [20]Moisés Blanco Calvo AF, Enrique Grande P, Rosario García C, Luís Antón A: Potential role of sugar transporters in cancer and their relationship with anticancer therapy. Int J Endocrinol 2010, 2010:14.
• [21]Ouwerkerk R, Jacobs MA, Macura KJ, Wolff AC, Stearns V, Mezban SD, Khouri NF, Bluemke DA, Bottomley PA: Elevated tissue sodium concentration in malignant breast lesions detected with non-invasive Na-23 MRI. Breast Cancer Res Treat 2007, 106(2):151-160.
• [22]Chen JQ, Contreras RG, Wang R, Fernandez SV, Shoshani L, Russo IH, Cereijido M, Russo J: Sodium/potasium ATPase (Na+, K+ − ATPase) and ouabain/related cardiac glycosides: a new paradigm for development of anti- breast cancer drugs? Breast Cancer Res Treat 2006, 96(1):1-15.
• [23]Wang ZG: Roles of K+ channels in regulating tumor cell proliferation and apoptosis. Pflugers Arch 2004, 448(3):274-286.
• [24]Huang Y, Anderle P, Bussey KJ, Barbacioru C, Shankavaram U, Dai Z, Reinhold WC, Papp A, Weinstein JN, Sadée W: Membrane transporters and channels: role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Res 2004, 15(64(12)):4294-4301.
• [25]Roussos ET, Condeelis JS, Patsialou A: Chemotaxis in cancer. Nat Rev Cancer 2011, 11(8):573-587.
• [26]Vinader V, Al-Saraireh Y, Wiggins HL, Rappoport JZ, Shnyder SD, Patterson LH, Afarinkia K: An agarose spot chemotaxis assay for chemokine receptor antagonists. J Pharmacol Toxicol Methods 2011, 64(3):213-216.
• [27]Wiggins HL, Rappoport JZ: An agarose spot assay for chemotactic invasion. Biotechniques 2010, 48(2):120-123.
• [28]Shackney SE: Tumor Growth, Cell Cycle Kinetics, and Cancer Treatment. McGraw Hill, New York; 1993.
• [29]Brú A, Pastor JM, Fernaud I, Brú I, Melle S, Berenguer C: Super-rough dynamics on tumor growth. Phys Rev Lett 1998, 81(18):4008-4011.
• [30]Brú A, Albertos S, Subiza JL, García-Asenjo JL, Brú I: The universal dynamics of tumor growth. Biophys J 2003, 85(5):2948-2961.