Abstract
With an approach to study the anti-tumor effects and mechanism of selenium compound, we investigated the anti-tumor activity and mechanism of Na5SeV5O18·3H2O (NaSeVO) in K562 cells. The results showed that 0.625≈20 mg/L NaSeVO could significantly inhibit the proliferation of K562 cellsin vitro in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay, the IC50 values were 14.41 (4.45-46.60) and 3.45 (2.29–5.22) mg/L after 48 h and 72 h treatment with NaSeVO respectively.In vivo experiments demonstrated that i.p. administration of 5, 10 mg/kg NaSeVO exhibited an significant inhibitory effect on the growth of transplantation tumor sarcoma 180 (S180) and hepatoma 22 (H22) in mice, with inhibition rate 26.8% and 58.4% on S180 and 31.3% and 47.4% on H22, respectively. Cell cycle studies indicated that the proportion of G0/G1 phase was increased at 2.5 mg/L while decreased at 10 mg/L after treatment for 24, 48 h. Whereas S phase was decreased at 2.5–5 mg/L and markedly increased at 10 mg/L after treatment for 48 h. After treatment for 24 h, 10 mg/L NaSeVO also markedly increased S and G2/M phases. Take together, the result clearly showed that NaSeVO markedly increased S and G2/M phases at 10 mg/L. The study of immunocytochemistry showed that the expression bcl-2 is significantly inhibited by 10 mg/L NaSeVO, and bax increased. Morphology observation also revealed typical apoptotic features. NaSeVO also significantly caused the accumulation of Ca2+ and Mg2+, reactive oxygen species (ROS) and the reduction of pH value and mitochondrial membrane potential in K562 cells as compared with control by confocal laser scanning microscope. These results suggest that NaSeVO has anti-tumor effects and its mechanism is attributed partially to apoptosis induced by the elevation of intracellular Ca2+, Mg2+ and ROS concentration, and a reduction of pH value and mitochondria membrane potential (MMP).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Benner, E., Bishop, M. R., Agarwal, N., Iversen, P., and Joshi, S. S., Combination of antisense oligonucleotide and low-dose chemotherapy in hematological malignancies.Pharmacol. Toxicol. Methods., 37, 229–235 (1997).
Bolduc, J. S., Denizeau, F., and Jumarie, C., Cadmium-induced mitochondrial membrane-potential dissipation does not necessarily require cytosolic oxidative stress: studies using rhodamine-123 fluorescence unquenching.Toxicol. Sci., 77, 299–306 (2004).
Burney, P. G., Comstock, G. W., and Morris, J. S., Pancreatic cancer.Clin. Nutr., 49, 895–900 (1997).
Cain, K., Inayat-Hussain, S. H., Kokileva, L., and Cohen, G. M., DNA cleavage in rat liver nuclei activated by Mg2+ or Ca2++Mg2+ is inhibited by a variety of structurally unrelated inhibitors.Biochem. Cell Biol., 72, 631–638 (1994).
Cotter, T. G. and Fernanded, R. S., Activation of a calcium magnesium independent endonuclease in human leukemic cell apoptosis.Anticancer Res., 13, 1253–1259 (1993).
El-Bayoumy, K., The protective role of selenium on genetic damage and cancer.Mutat. Res., 475, 123–139 (2001).
Foster, L. H. and Sumar, S., Selenium in health and disease: a review.Crit. Rev. Food Sci. Nutr., 37, 211–28 (1997).
Gasparian, A. V., Yao, Y. J., Lu, J., Yemelyanov, A. Y., Lyakh, L. A., Slaga, T. J. and Budunova, I. V., Selenium compounds inhibit 1κB Kinase (IKK) and Nuclear Factor-κB (NF-κB) in prostate cancer cells.Mol. Cancer Ther., 1, 1079–1087 (2002).
Glattre, E., Thomassen, Y., Haldorsen, T., Lund-Larsen, P. G., Theodorsen, L., and Aaseth, J., Prediagnostic serum selenium in a case-control study of thyroid cancer.Int. Epidemiol., 18, 45–49 (1989).
Huang, Y. L., Sheu, J. Y., and Lin, T. H., Association between oxidative stress and changes of trace elements in patients with breast cancer.Clin. Biochem., 32, 131–136 (1999).
Ip, C., Lessons from basic research in selenium and cancer prevention.Nutr., 128, 1845–1854 (1998).
Ip, C., Dong, Y., and Ganther, H. E., New concepts in selenium chemoprevention. Cancer Met. Rev., 21, 281–289 (2002).
Jacobson, M. D., Reactive oxygen species and programmed cell death.Trends Biochem. Sci., 21, 83–86 (1996).
Jaskiewicz, K., Marasas, W. F., Rossouw, J.E., Van Niekerk, F. E., and Heine Tech, E. W. P., Selenium and other mineral elements in populations at risk for esophageal cancer.Cancer, 62, 2635–2639 (1988).
Jung, U., Zheng, X.-X., Yoon, S.-O., and Chung, A.-S., Se-Methylselenocysteine induces apoptosis mediated by reactive oxygen species in HL-60 cells.Free Radic. Biology & Med., 31, 479–489 (2001).
Kamesaki, H., Mechanisms involved in chemotherapy-induced apoptosis and their implications in cancer chemotherapy.Int. Hematol., 68, 29–43 (1998).
Kornblau, S. M., The role of apoptosis in the pathogenesis, prognosis, and therapy of hematologic malignancies.Leukemia, 12, 41–46 (1998).
Lowe, S. W. and Lin, A. W., Apoptosis in cancer.Carcinogenesis, 21, 485–495 (2000).
McConkey, D. J., and Orrenius, S., The role of calcium in the regulation of apoptosis.Leukocyte. Biol., 59, 775–783 (1996).
Mosmann, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.Immunol.Methods., 65, 55–63 (1983).
Munaron, L., Antoniotti, S., Pla, A. F., and Lovisolo, D., Blocking Ca2+ entry: a way to control cell proliferation.Curr. Med. Chem., 12, 1533–1543 (2004).
Nicholls, D. G., and Ward, M. W., Mitochondrial membrane potential and neuronal glutamate excitotoxicity: mortality and millivolts.Trends Neurosci., 23, 166–174 (2000).
Philipov, P. and Tzatchev, K., Selenium concentrations in serum of patients with cerebral and extracerebral tumors.Zentralbl. Neurochir., 49, 344–347 (1988).
Rojas, E., Herrera, L. A., Poirier, L. A., and Ostrosky-Wegman, P., Are metals dietary carcinogens?Mutat. Res., 443, 157–181 (1999).
Shamberger, R. J., The genotoxicity of selenium.Mutat Res., 154, 29–48 (1985).
Shilo, S., Aronis, A., Komamitsky, R., and Tirosh, O., Selenite sensitizes mitochondrial permeability transition pore openingin vitro andin vivo: a possible mechanism for chemoprotection.Biochem., 370, 283–290 (2003).
Simon, S. M., Roy, D., and Schindler, M., Intracellular pH and the control of multidrug resistance.Proc. Natl. Acad. Sci., 91, 1128–1132 (1994).
Sinha, R., and El-Bayoumy, K., Apoptosis is a critical cellular event in cancer chemoprevention and chemotherapy by selenium compounds.Curr. Cancer Drug Targets, 4, 13–28 (2004).
Sinha, R., Bansal, M. P., Ganther, H., and Medina, D., Significance of selenium-labeled proteins for selenium’s chemopreventive functions.Carcinogenesis, 14, 1895–1900 (1993).
Wand, W. R.,In vivo methods. In Teicher, B.A. (Ed). Anticancer drug development guide, preclinical screening, clinical trials, and approval. Humana Press Inc., Totowa, NJ, pp. 59–213, (1997).
Wang H. T., Yang X. L., Zhang Z. H., Lu J. L., and Xu H. B., Reactive oxygen species from mitochondria mediate SW480 cells apoptosis induced by Na2SeO3.Biol. Trace Elem. Res., 85, 241–54 (2002).
Wang, X. W., Role of p53 and apoptosis in carcinogenesis.Anticancer Res., 19, 4759–4771 (1999).
Westin, T., Ahlbom, E., Johansson, E., Sandstrom, B., Karlberg, I., and Edstrom, S., Circulating levels of selenium and zinc in relation to nutritional status in patients with head and neck cancer.Arch. Otolaryngol. Head Neck Surg., 115, 1079–1082 (1989).
Zhong, W. and Oberley, T. D., Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line.Cancer Res., 61, 7071–7078 (2001).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yang, JY., Wang, ZR. The antitumor effects of selenium compound Na5SeV5O18·3H2O in K562 cell. Arch Pharm Res 29, 859–865 (2006). https://doi.org/10.1007/BF02973906
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02973906