Antiproliferative Effect of Electric Fields on Breast Tumor Cells In Vitro and In Vivo

Firman Alamsyah, Izzatun Niswah Ajrina, Fitriya Nur Annisa Dewi, Diah Iskandriati, Silvia Arin Prabandari, Warsito P. Taruno

Abstract


Our research focused on the antiproliferative effect of low intensity (18 Vpp) and intermediate frequency (100 KHz) electrostatic wave between two capacitive electrodes on breast tumor cells in vitro and in vivo. In vitro study has been conducted by using MCF-7 cell lines treated with external electrostatic for 24, 48, and 72 hours of treatment and the cells number were calculated during treatment by using hemocytometer and presented as Growth Inhibition (GI)% efficacy. For in vivo, we used female mice (Mus musculus) strain C3H as animal model. The mice were injected with either MCF-7 cells, mammary tumor cells from C3H donor, or NaCl 0.9% (placebo) subcutaneously into the axilla area and exposed by external electrostatic in each cage for 12 hours in 2 weeks before necropsied. The adjacent and breast tissue were collected and stained with Hematoxylin – Eosin then analyzed for histopathological profile. In vitro study revealed the number of exposed cells decreased with lower proliferation rate than the non-exposed cells. Moreover, the external electrostatic caused 28-39% growth inhibition efficacy of MCF-7 cells. After 2 weeks of exposure, placebo mice were physically normal, whereas the tumor undergone significant shrinkage of more than 67% in size. Histopathological analysis of the mammary glands indicated infiltration of macrophages into the tumor area through the blood vessel. No abnormality was found in the skin layer and mammary glands of the breast tissue of placebo mice. Here, we present new knowledge of electro-capacitive cancer therapy (ECCT) as a novel treatment modality.

Keywords : ECCT, tumor, in vitro, in vivo, breast cancer cells, antiproliferative


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References


Bethlem, H.L., 2002, Deceleration and Trapping of Polar Molecules Using Time-varying Electric Fields, Thesis, Katholieke Universiteit Nijmegen, Netherlands.

Binggeli, R. and Cameron, I.L., 1980, Cellular Potentials of Normal and Cancerous Fibroblasts and Hepatocytes, Cancer Res., 40, 1830-1835. Link

Brooker, R.J., Widmaier, E.P., Graham, L.E. and Stiling, P.D., 2008, Biology, McGraw Hill.

Dalton, C., Goater, A. D., Burt, J. P. and Smith, H. V., 2004, Analysis of Parasites by Electrorotation, J. Appl. Microbiol., 96(1), 24-32. CrossRef

Dujovne, I., van den Heuvel, M., Shen, Y., de Graaff, M. and Dekker, C., 2008, Velocity Modulation of Microtubules in Electric Fields, Nano Lett., 8(12), 4217-20. CrossRef

Kirson, E.D., Gurvich, Z. Schneiderman, R.D., Itzhaki, A., Wasserman, Y., et al., 2004, Disruption of Cancer Cell Replication by Alternating Electric Fields, Cancer Res., 64(9), 3288-3295. Link

Kirson, E. D., Dbaly, V., Tovarys, F., Vymazal, J., Soustiel, J. F., Itzhaki, A., et al., 2007, Alternating Electric Fields Arrest Cell Proliferation in Animal Tumor Models and Human Brain Tumors, Proc. Natl. Acad. Sci. U S A, 104(24), 10152-10157. CrossRef

Kirson, E.D., Schneiderman, R.S., Dbaly, V., Tovarys, F., Vymazal, J., Itzhaki, A., et al., 2009, Chemotherapeutic Treatment Efficacy and Sensitivity are Increased by Adjuvant Alternating Electric Fields (TTFields), BMC Med. Phys., 9,1. CrossRef

Lee, S.H., Choi, E.H., Feingold, K.R., Jiang, S. and Ahn, S.K., 1998, Iontophoresis Itself on Hairless Mouse Skin Induces the Loss of the Epidermal Calcium Gradient Without Skin Barrier Impairment, J. Invest. Dermatol., 111(1), 39-43. CrossRef

Leslie, A., Carey, F.A., Pratt, N.R. and Steele, R.J.C., 2002, The Colorectal Adenoma-Carcinoma Sequence, Br. J. Surg., 89(7), 845-860. CrossRef

Ma, W., Shi, T., Tang, Z., Liu, S., Malik, R. and Zhang, L., 2011, High-throughput Dielectrophoretic Manipulation of Bioparticles Within Fluids Through Biocompatible Three-Dimensional Microelectrode Array, Electrophoresis, 32(5), 494-505. CrossRef

Mahaworasilpa, T. L., Coster, H. G. L. and George, E. P., 1996, Forces on Biological Cells Due to Applied Alternating (AC) Electric Fields, Biochim. Biophys. Acta., 1193(1), 118-126. Link

Mursilatun, 2010,The Effect of External Electric Field ECCT on Breast Cancer Cell Proliferation (MVF-7), Thesis, Dept. of Physics University of Indonesia, Jakarta.

Pasquier, E. and Kavallaris, M., 2007, Microtubules: a Moving Target in Cancer Therapy, IUBMB lIFE, 60(3), 165-70. CrossRef

Qiao, G., Duan, W., Chatwin, C., Sinclair, A. and Wang, W., 2010, Electrical Properties of Breast Cancer Cells from Impedance Measurement of Cell Suspensions, J. Phys.: Conf. Ser 224, CrossRef

Sabrina, Q., 2014,Effect of Electric Field Treatment Variation Against Lethal Level Cell Line MCF-7 (human breast cancer) in Vitro and Measurement of Cell Capacitance Value, Thesis, Dept. of Physics University of Indonesia, Jakarta.

Shinomiya, N., 2001, New Concepts in Radiation-Induced Apoptosis: 'Premitotic Apoptosis' and 'Postmitotic Apoptosis', J. Cell. Mol. Med., 5(3), 240-253. Link

Takashima, S. and Schwan, H.P., 1985, Alignment of Microscopic Particles in Electric Fields and Its Biological Implications, Biophys. J., 47, 513-518. CrossRef

Teo, Z.Y.P., 2003, The Role of Macrophages in Apoptosis; Initiator, Regulator, Scavenger, Reviews in Undergraduate Res., 2, 7-11. Link

Tsutsui, H. and Ho, C.M., 2009, Cell Separation by Non-inertial Force Fields in Microfluidic Systems, Mech. Res. Commun., 36(1), 92-103. CrossRef

Weigert, A., Tzieply, N., Von Knethen, A., Johann, A. M., Schmidt, H., Geisslinger, G. et al., 2007, Tumor Cell Apoptosis Polarizes Macrophages – Role of Sphingosine-1-phosphate, Mol. Biol. Cell, 18(10), 3810-3819. CrossRef

Zhao, M., Forrester, J.V. and McCaig, C.D., 1999, A Small, Physiological Electric Field Orients Cell Division, Proc. Natl. Acad. Sci. USA, 96(9), 4942–4946. Link

Zimmermann, U., Vienken, J. and Pilwat, G., 1981, Rotation of Cells in Alternating Electric Field: The Occurrence of a Resonance Frequency, Z. Naturforsch C., 36(1-2), 173-177. Link




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev6iss3pp71-77

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