Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

Frajese,Giovanni  Vanni; Benvenuto,Monica; Fantini,Massimo; Ambrosin,Elena; Sacchetti,Pamela; Masuelli,Laura; Giganti,Maria  Gabriella; Modesti,Andrea; Bei,Roberto

doi:10.3892/ol.2016.4506

June-2016 Volume 11 Issue 6

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

June-2016 Volume 11 Issue 6

Full Size Image

Article

Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

Authors:
- Giovanni Vanni Frajese
- Monica Benvenuto
- Massimo Fantini
- Elena Ambrosin
- Pamela Sacchetti
- Laura Masuelli
- Maria Gabriella Giganti
- Andrea Modesti
- Roberto Bei
View Affiliations / Copyright

Affiliations: Department of Sports Science, Human and Health, University of Rome ‘Foro Italico’, Rome I‑00135, Italy, Department of Clinical Sciences and Translational Medicine, University of Rome ‘Tor Vergata’, Rome I‑00133, Italy, Department of Experimental Medicine, University of Rome ‘Sapienza’, Rome I‑00185, Italy
Pages: 4224-4234
|
Published online on: April 27, 2016

https://doi.org/10.3892/ol.2016.4506
Expand metrics +

Abstract

Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub‑G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF‑7, A+K induced the appearance of the 18 kDa isoform of B‑cell lymphoma‑2‑associated X protein (Bax), which is a more potent inducer of apoptosis than the full‑length Bax‑p21. The effects of A and K on the phosphorylation of extracellular signal‑regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor‑κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro.

View Figures

View References

1.	Khaw KT, Bingham S, Welch A, Luben R, Wareham N, Oakes S and Day N: Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: A prospective population study. European Prospective Investigation into Cancer and Nutrition. Lancet. 357:657–663. 2001. View Article : Google Scholar : PubMed/NCBI
2.	Block G: Epidemiologic evidence regarding vitamin C and cancer. Am J Clin Nutr. 54(Suppl 6): 1310S–1314S. 1991.PubMed/NCBI
3.	Cameron E and Pauling L: The orthomolecular treatment of cancer. I. The role of ascorbic acid in host resistance. Chem Biol Interact. 9:273–283. 1974. View Article : Google Scholar : PubMed/NCBI
4.	Creagan ET, Moertel CG, O'Fallon JR, Schutt AJ, O'Connell MJ, Rubin J and Frytak S: Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med. 301:687–690. 1979. View Article : Google Scholar : PubMed/NCBI
5.	Ohno S, Ohno Y, Suzuki N, Soma G and Inoue M: High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Anticancer Res. 29:809–815. 2009.PubMed/NCBI
6.	Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J and Cantilena LR: Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc Natl Acad Sci USA. 93:3704–3709. 1996. View Article : Google Scholar : PubMed/NCBI
7.	Levine M, Wang Y, Padayatty SJ and Morrow J: A new recommended dietary allowance of vitamin C for healthy young women. Proc Natl Acad Sci USA. 98:9842–9846. 2001. View Article : Google Scholar : PubMed/NCBI
8.	Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA and Levine M: Vitamin C pharmacokinetics: Implications for oral and intravenous use. Ann Intern Med. 140:533–537. 2004. View Article : Google Scholar : PubMed/NCBI
9.	Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, Rousseau C, Robitaille L and Miller WH Jr: Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol. 19:1969–1974. 2008. View Article : Google Scholar : PubMed/NCBI
10.	Parrow NL, Leshin JA and Levine M: Parenteral ascorbate as a cancer therapeutic: A reassessment based on pharmacokinetics. Antioxid Redox Signal. 19:2141–2156. 2013. View Article : Google Scholar : PubMed/NCBI
11.	Ma Y, Chapman J, Levine M, Polireddy K, Drisko J and Chen Q: High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 6:222ra182014. View Article : Google Scholar : PubMed/NCBI
12.	Cone CD Jr: Unified theory on the basic mechanism of normal mitotic control and oncogenesis. J Theor Biol. 30:151–181. 1971. View Article : Google Scholar : PubMed/NCBI
13.	Hughes FM Jr and Cidlowski JA: Potassium is a critical regulator of apoptotic enzymes in vitro and in vivo. Adv Enzyme Regul. 39:157–171. 1999. View Article : Google Scholar : PubMed/NCBI
14.	Wang Z: Roles of K⁺ channels in regulating tumour cell proliferation and apoptosis. Pflugers Arch. 448:274–286. 2004. View Article : Google Scholar : PubMed/NCBI
15.	DeCoursey TE, Chandy KG, Gupta S and Cahalan MD: Voltage-gated K⁺ channels in human T lymphocytes: A role in mitogenesis? Nature. 307:465–468. 1984. View Article : Google Scholar : PubMed/NCBI
16.	Pardo LA: Voltage-gated potassium channels in cell proliferation. Physiology (Bethesda). 19:285–292. 2004. View Article : Google Scholar : PubMed/NCBI
17.	Wonderlin WF and Strobl JS: Potassium channels, proliferation and G1 progression. J Membr Biol. 154:91–107. 1996. View Article : Google Scholar : PubMed/NCBI
18.	Boros LG, Lee PW, Brandes JL, Cascante M, Muscarella P, Schirmer WJ, Melvin WS and 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. 50:55–59. 1998. View Article : Google Scholar : PubMed/NCBI
19.	Smith NK, Stabler SB, Cameron IL and Medina D: X-Ray microanalysis of electrolyte content of normal, preneoplastic, and neoplastic mouse mammary tissue. Cancer Res. 41:3877–3880. 1981.PubMed/NCBI
20.	Arrebola F, Fernández-Segura E, Campos A, Crespo PV, Skepper JN and Warley A: Changes in intracellular electrolyte concentrations during apoptosis induced by UV irradiation of human myeloblastic cells. Am J Physiol Cell Physiol. 290:C638–C649. 2006. View Article : Google Scholar : PubMed/NCBI
21.	Mobasheri A, Fox R, Evans I, Cullingham F, Martín-Vasallo P and Foster CS: Epithelial Na, K-ATPase expression is down-regulated in canine prostate cancer; a possible consequence of metabolic transformation in the process of prostate malignancy. Cancer Cell Int. 3:82003. View Article : Google Scholar : PubMed/NCBI
22.	Chen JQ, Contreras RG, Wang R, Fernandez SV, Shoshani L, Russo IH, Cereijido M and Russo J: Sodium/potassium ATPase (Na⁺, K⁺-ATPase) and ouabain/related cardiac glycosides: A new paradigm for development of anti-breast cancer drugs? Breast Cancer Res Treat. 96:1–15. 2006. View Article : Google Scholar : PubMed/NCBI
23.	Parkinson GN, Lee MP and Neidle S: Crystal structure of parallel quadruplexes from human telomeric DNA. Nature. 417:876–880. 2002. View Article : Google Scholar : PubMed/NCBI
24.	Salvati E, Rizzo A, Iachettini S, Zizza P, Cingolani C, D'Angelo C, Porru M, Mondello C, Aiello A, Farsetti A, et al: A basal level of DNA damage and telomere deprotection increases the sensitivity of cancer cells to G-quadruplex interactive compounds. Nucleic Acids Res. 43:1759–1769. 2015. View Article : Google Scholar : PubMed/NCBI
25.	Dai J, Carver M and Yang D: Polymorphism of human telomeric quadruplex structures. Biochimie. 90:1172–1183. 2008. View Article : Google Scholar : PubMed/NCBI
26.	Kelland LR: Overcoming the immortality of tumour cells by telomere and telomerase based cancer therapeutics - current status and future prospects. Eur J Cancer. 41:971–979. 2005. View Article : Google Scholar : PubMed/NCBI
27.	Paoli G: The Bio-magnetic nature of cancer and the role of potassium ascorbate and ribose against cellar degeneration. J Nucl Energy. 7:114–119. 2003.
28.	Croci S, Pedrazzi G, Passeri G, Delsignore R and Ortalli I: Red cell Hb oxidation of healthy subjects compared to breast cancer patients. Anticancer Res. 22:2903–2906. 2002.PubMed/NCBI
29.	Croci S, Pedrazzi G, Passeri G, Piccolo P and Ortalli I: Acetylphenylhydrazine induced haemoglobin oxidation in erythrocytes studied by Mössbauer spectroscopy. Biochim Biophys Acta. 1568:99–104. 2001. View Article : Google Scholar : PubMed/NCBI
30.	Croci S, Bruni L, Bussolati S, Castaldo M and Dondi M: Potassium bicarbonate and D-ribose effects on A72 canine and HTB-126 human cancer cell line proliferation in vitro. Cancer Cell Int. 11:302011. View Article : Google Scholar : PubMed/NCBI
31.	Masuelli L, Marzocchella L, Quaranta A, Palumbo C, Pompa G, Izzi V, Canini A, Modesti A, Galvano F and Bei R: Apigenin induces apoptosis and impairs head and neck carcinomas EGFR/ErbB2 signaling. Front Biosci (Landmark Ed). 16:1060–1068. 2011. View Article : Google Scholar : PubMed/NCBI
32.	Masuelli L, Marzocchella L, Focaccetti C, Tresoldi I, Palumbo C, Izzi V, Benvenuto M, Fantini M, Lista F, Tarantino U, et al: Resveratrol and diallyl disulfide enhance curcumin-induced sarcoma cell apoptosis. Front Biosci (Landmark Ed). 17:498–508. 2012. View Article : Google Scholar : PubMed/NCBI
33.	Bei R, Masuelli L, Moriconi E, Visco V, Moretti A, Kraus MH and Muraro R: Immune responses to all ErbB family receptors detectable in serum of cancer patients. Oncogene. 18:1267–1275. 1999. View Article : Google Scholar : PubMed/NCBI
34.	Bei R, Budillon A, Masuelli L, Cereda V, Vitolo D, Di Gennaro E, Ripavecchia V, Palumbo C, Ionna F, Losito S, et al: Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patients. J Pathol. 204:317–325. 2004. View Article : Google Scholar : PubMed/NCBI
35.	Faggioni G, Pomponi A, De Santis R, Masuelli L, Ciammaruconi A, Monaco F, Di Gennaro A, Marzocchella L, Sambri V, Lelli R, et al: West Nile alternative open reading frame (N-NS4B/WARF4) is produced in infected West Nile Virus (WNV) cells and induces humoral response in WNV infected individuals. Virol J. 9:2832012. View Article : Google Scholar : PubMed/NCBI
36.	Masuelli L, Budillon A, Marzocchella L, Mrozek MA, Vitolo D, Di Gennaro E, Losito S, Sale P, Longo F, Ionna F, et al: Caveolin-1 overexpression is associated with simultaneous abnormal expression of the E-cadherin/α-β catenins complex and multiple ErbB receptors and with lymph nodes metastasis in head and neck squamous cell carcinomas. J Cell Physiol. 227:3344–3353. 2012. View Article : Google Scholar : PubMed/NCBI
37.	Masuelli L, Bei R, Sacchetti P, Scappaticci I, Francalanci P, Albonici L, Coletti A, Palumbo C, Minieri M, Fiaccavento R, et al: Beta-catenin accumulates in intercalated disks of hypertrophic cardiomyopathic hearts. Cardiovasc Res. 60:376–387. 2003. View Article : Google Scholar : PubMed/NCBI
38.	Masuelli L, Pompa G, Fabrizi M, Quaranta A, Vozza I, Piccoli L, Antonelli A, Marzocchella L, Di Carlo S, Perrotti V, et al: Patients with peri-implantitis, unlike those with a healthy periimplant microenvironment, display antibodies to more than one heat shock protein (HSP 27, HSP 65 and HSP 90) linear epitope. Eur J Inflamm. 9:257–267. 2011.
39.	Ingrosso G, Fantini M, Nardi A, Benvenuto M, Sacchetti P, Masuelli L, Ponti E, Frajese GV, Lista F, Schillaci O, et al: Local radiotherapy increases the level of autoantibodies to ribosomal P0 protein but not to heat shock proteins, extracellular matrix molecules and EGFR/ErbB2 receptors in prostate cancer patients. Oncol Rep. 29:1167–1174. 2013.PubMed/NCBI
40.	Palumbo C, Albonici L, Bei R, Bocci C, Scarpa S, Di Nardo P and Modesti A: HMBA induces cell death and potentiates doxorubicin toxicity in malignant mesothelioma cells. Cancer Chemother Pharmacol. 54:398–406. 2004. View Article : Google Scholar : PubMed/NCBI
41.	Toyota H, Yanase N, Yoshimoto T, Moriyama M, Sudo T and Mizuguchi J: Calpain-induced Bax-cleavage product is a more potent inducer of apoptotic cell death than wild-type Bax. Cancer Lett. 189:221–230. 2003. View Article : Google Scholar : PubMed/NCBI
42.	Du J, Cullen JJ and Buettner GR: Ascorbic acid: Chemistry, biology and the treatment of cancer. Biochim Biophys Acta. 1826:443–457. 2012.PubMed/NCBI
43.	Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E and Levine M: Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA. 102:13604–13609. 2005. View Article : Google Scholar : PubMed/NCBI
44.	Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang SH, Taghiyev AF, Du C, Knudson CM and Cullen JJ: Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. Clin Cancer Res. 16:509–520. 2010. View Article : Google Scholar : PubMed/NCBI
45.	Chen P, Yu J, Chalmers B, Drisko J, Yang J, Li B and Chen Q: Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy. Anticancer Drugs. 23:437–444. 2012. View Article : Google Scholar : PubMed/NCBI
46.	Martinovich GG, Golubeva EN, Martinovich IV and Cherenkevich SN: Redox regulation of calcium signaling in cancer cells by ascorbic acid involving the mitochondrial electron transport chain. J Biophys. 2012:9216532012. View Article : Google Scholar : PubMed/NCBI
47.	Han SS, Kim K, Hahm ER, Lee SJ, Surh YJ, Park HK, Kim WS, Jung CW, Lee MH, Park K, et al: L-ascorbic acid represses constitutive activation of NF-kappaB and COX-2 expression in human acute myeloid leukemia, HL-60. J Cell Biochem. 93:257–270. 2004. View Article : Google Scholar : PubMed/NCBI
48.	Park S, Ahn ES, Lee S, Jung M, Park JH, Yi SY and Yeom CH: Proteomic analysis reveals upregulation of RKIP in S-180 implanted BALB/C mouse after treatment with ascorbic acid. J Cell Biochem. 106:1136–1145. 2009. View Article : Google Scholar : PubMed/NCBI
49.	Ranzato E, Biffo S and Burlando B: Selective ascorbate toxicity in malignant mesothelioma: A redox Trojan mechanism. Am J Respir Cell Mol Biol. 44:108–117. 2011. View Article : Google Scholar : PubMed/NCBI
50.	Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, Shacter E, Choyke PL, Pooput C, Kirk KL, Buettner GR and Levine M: Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci USA. 104:8749–8754. 2007. View Article : Google Scholar : PubMed/NCBI
51.	Cha J, Roomi MW, Ivanov V, Kalinovsky T, Niedzwiecki A and Rath M: Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice. Int J Oncol. 42:55–64. 2013.PubMed/NCBI
52.	Kim JE, Cho HS, Yang HS, Jung DJ, Hong SW, Hung CF, Lee WJ and Kim D: Depletion of ascorbic acid impairs NK cell activity against ovarian cancer in a mouse model. Immunobiology. 217:873–881. 2012. View Article : Google Scholar : PubMed/NCBI
53.	Riordan HD, Riordan NH, Jackson JA, Casciari JJ, Hunninghake R, González MJ, Mora EM, Miranda-Massari JR, Rosario N and Rivera A: Intravenous vitamin C as a chemotherapy agent: A report on clinical cases. P R Health Sci J. 23:115–118. 2004.PubMed/NCBI
54.	Shimpo K, Nagatsu T, Yamada K, Sato T, Niimi H, Shamoto M, Takeuchi T, Umezawa H and Fujita K: Ascorbic acid and adriamycin toxicity. Am J Clin Nutr. 54(Suppl 6): 1298S–1301S. 1991.PubMed/NCBI
55.	Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L and Beuth J: Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: Results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo. 25:983–990. 2011.PubMed/NCBI
56.	L'Allemain G, Paris S and Pouysségur J: Growth factor action and intracellular pH regulation in fibroblasts. Evidence for a major role of the Na⁺/H⁺ antiport. J Biol Chem. 259:5809–5815. 1984.PubMed/NCBI
57.	Gerson DF, Kiefer H and Eufe W: Intracellular pH of mitogen-stimulated lymphocytes. Science. 216:1009–1010. 1982. View Article : Google Scholar : PubMed/NCBI
58.	Bruni L, Babarinde AA, Ortalli I and Croci S: K-D:rib dampens Hs 578T cancer cell chemoinvasion and proliferation. Cancer Cell Int. 14:772014. View Article : Google Scholar : PubMed/NCBI
59.	Lacroix M, Toillon RA and Leclercq G: p53 and breast cancer, an update. Endocr Relat Cancer. 13:293–325. 2006. View Article : Google Scholar : PubMed/NCBI
60.	Subik K, Lee JF, Baxter L, Strzepek T, Costello D, Crowley P, Xing L, Hung MC, Bonfiglio T, Hicks DG and Tang P: The expression patterns of ER, PR, HER2, CK5/6, EGFR, Ki-67 and AR by immunohistochemical analysis in breast cancer cell lines. Breast Cancer (Auckl). 4:35–41. 2010.PubMed/NCBI
61.	Sun D, Lopez-Guajardo CC, Quada J, Hurley LH and Von Hoff DD: Regulation of catalytic activity and processivity of human telomerase. Biochemistry. 38:4037–4044. 1999. View Article : Google Scholar : PubMed/NCBI
62.	Harley CB, Futcher AB and Greider CW: Telomeres shorten during ageing of human fibroblasts. Nature. 345:458–460. 1990. View Article : Google Scholar : PubMed/NCBI
63.	Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL and Shay JW: Specific association of human telomerase activity with immortal cells and cancer. Science. 266:2011–2015. 1994. View Article : Google Scholar : PubMed/NCBI
64.	Zahler AM, Williamson JR, Cech TR and Prescott DM: Inhibition of telomerase by G-quartet DNA structures. Nature. 350:718–720. 1991. View Article : Google Scholar : PubMed/NCBI
65.	Hurley LH: DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer. 2:188–200. 2002. View Article : Google Scholar : PubMed/NCBI
66.	Neidle S and Parkinson G: Telomere maintenance as a target for anticancer drug discovery. Nat Rev Drug Discov. 1:383–393. 2002. View Article : Google Scholar : PubMed/NCBI
67.	Hurley LH, Wheelhouse RT, Sun D, Kerwin SM, Salazar M, Fedoroff OY, Han FX, Han H, Izbicka E and Von Hoff DD: G-quadruplexes as targets for drug design. Pharmacol Ther. 85:141–158. 2000. View Article : Google Scholar : PubMed/NCBI
68.	Redon S, Bombard S, Elizondo-Riojas MA and Chottard JC: Platinum cross-linking of adenines and guanines on the quadruplex structures of the AG₃(T₂AG₃)₃ and (T₂AG₃)₄ human telomere sequences in Na⁺ and K⁺ solutions. Nucleic Acids Res. 31:1605–1613. 2003. View Article : Google Scholar : PubMed/NCBI
69.	Phan AT and Patel DJ: Two-repeat human telomeric d(TAGGGTTAGGGT) sequence forms interconverting parallel and antiparallel G-quadruplexes in solution: Distinct topologies, thermodynamic properties, and folding/unfolding kinetics. J Am Chem Soc. 125:15021–15027. 2003. View Article : Google Scholar : PubMed/NCBI
70.	Li J, Correia JJ, Wang L, Trent JO and Chaires JB: Not so crystal clear: The structure of the human telomere G-quadruplex in solution differs from that present in a crystal. Nucleic Acids Res. 33:4649–4659. 2005. View Article : Google Scholar : PubMed/NCBI
71.	Włodarczyk A, Grzybowski P, Patkowski A and Dobek A: Effect of ions on the polymorphism, effective charge, and stability of human telomeric DNA. Photon correlation spectroscopy and circular dichroism studies. J Phys Chem B. 109:3594–3605. 2005. View Article : Google Scholar : PubMed/NCBI
72.	Ambrus A, Chen D, Dai J, Bialis T, Jones RA and Yang D: Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution. Nucleic Acids Res. 34:2723–2735. 2006. View Article : Google Scholar : PubMed/NCBI
73.	Dai J, Carver M, Punchihewa C, Jones RA and Yang D: Structure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K⁺ solution: Insights into structure polymorphism of the human telomeric sequence. Nucleic Acids Res. 35:4927–4940. 2007. View Article : Google Scholar : PubMed/NCBI
74.	Hadi SM, Ullah MF, Shamim U, Bhatt SH and Azmi AS: Catalytic therapy of cancer by ascorbic acid involves redox cycling of exogenous/endogenous copper ions and generation of reactive oxygen species. Chemotherapy. 56:280–284. 2010. View Article : Google Scholar : PubMed/NCBI