Impact of inhomogeneous static magnetic field (31.7-232.0 mT) exposure on human neuroblastoma SH-SY5Y cells during cisplatin administration (original) (raw)

Combination of static magnetic field and cisplatin in order to reduce drug resistance in cancer cell lines

International Journal of Radiation Biology, 2019

Purpose: In this study, the effects of different intensities of Static Magnetic Fields (SMFs) (10, 15 and 25 mT) and different concentrations of cisplatin drug were investigated on the viability percent and IC 50 of the A2780 and A2780-CP cell lines at 24, 48 and 96 hours to show useful potential of SMF as a physical agent to enhance the effectiveness of common therapeutic approaches and decrease of drug resistance to cisplatin anticancer drug. Materials and methods: Magnetic field exposure was performed using a locally designed generator. The cell viability percent, IC 50 and cisplatin uptake in treated cells were evaluated by MTT assay and inductively coupled plasma (ICP), respectively. Results: Increasing of concentration and time of cisplatin drug showed a noticeable decrease in viability percent in sensitive and resistant cell lines compare with control group. These decreases were more significant in resistant cells compared with sensitive cells. The obtained IC 50 values for resistant were greater than the values obtained for A2780 cells. ICP analysis demonstrated an increased uptake of cisplatin after treatment for 48 and 96 h relative to untreated groups in both resistant and sensitive cells. Conclusion: Results showed that A2780 cells were more sensitive to cisplatin than A2780-CP. Studies have shown that SMF can increase the effect of cisplatin on cell viability percent and decrease the resistance of A2780-CP cells by producing large, verruca shaped structures at the surface of the cell membrane.

Static magnetic fields affect calcium fluxes and inhibit stress-induced apoptosis in human glioblastoma cells

Cytometry, 2002

Background: Epidemiologic data revealed increased brain tumor incidence in workers exposed to magnetic fields (MFs), raising concerns about the possible link between MF exposure and cancer. However, MFs seem to be neither mutagenic nor tumorigenic. The mechanism of their tumorigenic effect has not been elucidated. Methods: To evaluate the interference of MFs with physical (heat shock, HS) and chemical (etoposide, VP16) induced apoptoses, respectively, we exposed a human glioblastoma primary culture to 6 mT static MF. We investigated cytosolic Ca 2ϩ ([Ca 2ϩ ] i ) fluxes and extent of apoptosis as key endpoints. The effect of MFs on HS-and VP16-induced apoptoses in primary glioblastoma cultures from four patients was also tested. Results: Static MFs increased the [Ca 2ϩ ] i from a basal value of 124 Ϯ 4 nM to 233 Ϯ 43 nM (P Ͻ 0.05). MF exposure dramatically reduced the extent of HS-and VP16-induced apoptoses in all four glioblastoma primary cultures analyzed by 56% (range, 28 -87%) and 44% (range, 38 -48%), respectively. However, MF alone did not exert any apoptogenic activity. Differences were observed across the four cultures with regard to apoptotic induction by HS and VP16 and to MF apoptotic reduction, with an individual variability with regard to apoptotic sensitivity. Conclusion: The ability of static MFs to reduce the extent of damage-induced apoptosis in glioblastoma cells might allow the survival of damaged and possibly mutated cells.

Cytotoxicity Changes of Cisplatin Drug in the Presence of Magnetic Fields

2006

The aim of the present work is to study the cytotox icity of cisplatin in the presence of magnetic fields. For this purpose an exposure sy stem capable of producing static and alternating magnetic fields in horizontal area of 30 ×20 cm 2 was built. Eighty mice were grouped equally into fo ur groups namely GI, GII, GIII and GIV. Animals of group GI were used as control (sham exposed), animals of GII were exposed to a combined static and alternating magnetic fields of 3.6 mT for 35 min/day, 6 day/week for 21 days, animals of GIII were injected with cisplatin (3 mg/kg) and sham exposed to magnetic fields, the final group GIV wer e injected with cisplatin (3 mg/kg) and exposed to magnetic fields as GII. The induced changes in sple en and kidney were carried out through the calculation of the relative spleen weights and dete rmination of DNA content of the kidney and its ultrastructure changes. The results indicated a dec rease in the relative spleen weights with a decreas e in the growt...

Anticancer Effects of Moderate Static Magnetic Field on Cancer Cells In Vitro

Research in Molecular Medicine, 2019

Background: Expansion of the use of magnetic fields in metals, mining, transport, research, and medicine industries has led to a discussion about the effects of magnetic fields and whether their strength is negligible. The aim of this study was to investigate the effects of magnetic field on the viability and proliferation rate of HeLa cells. Materials and Methods: We studied the effects of magnetic field on the viability, proliferation rate and membrane lipid peroxidation of cells, thus, HeLa cells (cancer cells) and human fibroblast cells (normal cells) were used. Initially, the cells were cultured in DMEM and to determine the impact of the magnetic field, the cells were treated with magnetic field at 4 specific intensity levels (0, 7, 14 and 21 mT) and 2 exposure times (24 h and 48 h). The viability percentage and inhibition of cell proliferation were calculated by MTT assay and Trypan blue staining, respectively. Results: Lipid peroxidation of the cell membrane was examined by m...

Static and ELF magnetic fields enhance the in vivo anti-tumor efficacy of cis-platin against lewis lung carcinoma, but not of cyclophosphamide against B16 melanotic melanoma

Pharmacological Research, 2003

Previous works showed that exposure to static and extremely low frequency (ELF) magnetic fields (MF) over 3 mT slows down the growth kinetics of human tumors engrafted s.c. in immunodeficient mice, reducing their metastatizing power and prolonging mouse survival. In the experiments reported here, immunocompetent mice bearing murine Lewis Lung carcinomas (LLCs) or B16 melanotic melanomas were exposed to MF and treated respectively with two commonly used anti-cancer drugs: cis-diamminedichloroplatinum (cis-platin) and N,N-bis (2-chloroethyl)tetra-hydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide (cyclophosphamide). The experiment endpoint was survival time. The survival time of mice treated with cis-platin (3 mg/kg i.p.) and exposed to MF was significantly (P < 0.01) longer than that of mice treated only with cis-platin or only exposed to MF, superimposing that of mice treated with 10 mg/kg i.p. of the drug, showing that MF act synergically with the pharmacological treatment. On the contrary, when mice treated with cyclophosphamide (50 mg/kg i.p.) were exposed to MF no synergic effects were observed, the survival curve being exactly the same as that of mice treated with the drug alone. No clinical signs or toxicity were seen in any of the mice exposed to MF alone or along with cis-platin or cyclophosphamide treatment, compared to mice given only the two known drugs. A possible explanation for the synergic effect of MF being found in mice treated with cis-platin could be that the platinum ion stimulates radical production and that MF enhance active oxygen production bringing about changes in tumor cell membrane permeability, influencing positively the drug uptake. Alternatively, or in addition to this, it has been demonstrated that the rate of conversion of cis-platin to reactive species able to bind to DNA, is increased by localized production of free radicals by MF.

Bioeffects of Static Magnetic Fields: Oxidative Stress, Genotoxic Effects, and Cancer Studies

BioMed Research International, 2013

The interaction of static magnetic fields (SMFs) with living organisms is a rapidly growing field of investigation. The magnetic fields (MFs) effect observed with radical pair recombination is one of the well-known mechanisms by which MFs interact with biological systems. Exposure to SMF can increase the activity, concentration, and life time of paramagnetic free radicals, which might cause oxidative stress, genetic mutation, and/or apoptosis. Current evidence suggests that cell proliferation can be influenced by a treatment with both SMFs and anticancer drugs. It has been recently found that SMFs can enhance the anticancer effect of chemotherapeutic drugs; this may provide a new strategy for cancer therapy. This review focuses on our own data and other data from the literature of SMFs bioeffects. Three main areas of investigation have been covered: free radical generation and oxidative stress, apoptosis and genotoxicity, and cancer. After an introduction on SMF classification and m...

Molecular basis underlying the biological effects elicited by extremely low-frequency magnetic field (ELF-MF) on neuroblastoma cells

Journal of Cellular Biochemistry, 2011

Extremely low-frequency magnetic fields (ELF-MFs) may affect human health because of the possible associations with leukemia but also with cancer, cardiovascular, and neurological disorders. In the present work, human SH-SY5Y neuroblastoma cells were exposed to a 50 Hz, 1 mT sinusoidal ELF-MF at three different times, that is, 5 days (T5), 10 days (T10), and 15 days (T15) and then the effects of ELF-MF on proteome expression and biological behavior were investigated. Through comparative analysis between treated and control samples, we analyzed the proteome changes induced by ELF-MF exposure. Nine new proteins resolved in sample after a 15-day treatment were involved in a cellular defense mechanism and/or in cellular organization and proliferation such as peroxiredoxin isoenzymes (2, 3, and 6), 3-mercaptopyruvate sulfurtransferase, actin cytoplasmatic 2, t-complex protein subunit beta, ropporin-1A, and profilin-2 and spindlin-1. Our results indicated that ELF-MFs exposure altered the proliferative status and other important cell biology-related parameters, such as cell growth pattern, and cytoskeletal organization. These findings support our hypothesis that ELF radiation could trigger a shift toward a more invasive phenotype.

The antitumor effect of static and extremely low frequency magnetic fields against nephroblastoma and neuroblastoma

Bioelectromagnetics, 2018

Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of th...

Static and ELF magnetic fields induce tumor growth inhibition and apoptosis

Bioelectromagnetics, 2001

The ability of static and extremely low frequency (ELF) Magnetic Fields (MF) to interfere with neoplastic cell function has been evaluated. In vitro experiments were carried out to study the role of MF characteristics (intensity, frequency, and modulation) on two transformed cell lines (WiDr human colon adenocarcinoma and MCF-7 human breast adenocarcinoma) and one nontransformed cell line (MRC-5 embryonal lung ®broblast). Increase in cell death morphologically consistent with apoptosis was reported exclusively in the two transformed cell lines. Cell-death induction was observed with MF of more than 1 mT. It was independent of the MF frequency and increased when modulated MF (static with a superimposition of ELF at 50 Hz) were used. Based on the in vitro results, four different MF exposure characteristics were selected and used to treat nude mice xenografted with WiDr cells. The treatment of nude mice bearing WiDr tumors subcutaneously. with daily exposure for 70 min to MF for 4 weeks caused signi®cant tumor growth inhibition (up to 50%) by the end of the treatment when modulated MF were used for at least 60% of the whole treatment period and the time-averaged total MF intensity was higher than 3.59 mT. No toxic morphological changes induced by exposure were observed in renewing, slowly proliferating, or static normal cells. A discussion on the possible biophysical mechanism at the base of the observed biological results is also offered. Bioelectromagnetics 22:419±428, 2001.

Exposure to strong static magnetic field slows the growth of human cancer cells in vitro

Bioelectromagnetics, 1996

Proposals to enhance the amount of radiation dose delivered to small tumors with radioimmunotherapy by constraining emitted electrons with very strong homogeneous static magnetic fields has renewed interest in the cellular effects of prolonged exposures to such fields. Past investigations have not studied the effects on tumor cell growth of lengthy exposures to very high magnetic fields. Three malignant human cell lines, HTB 63 (melanoma), HTB 77 IP3 (ovarian carcinoma), and CCL 86 (lymphoma; Raji cells), were exposed to a 7 Tesla uniform static magnetic field for 64 hours. Following exposure, the number of viable cells in each group was determined. In addition, multicycle flow cytometry was performed on all cell lines, and pulsed-field electrophoresis was performed solely on Raji cells to investigate changes in cell cycle patterns and the possibility of DNA fragmentation induced by the magnetic field. A 64 h exposure to the magnetic field produced a reduction in viable cell number in each of the three cell lines. Reductions of 19.04 k 7.3296, 22.06 k 6.19%, and 40.68 ? 8.31 % were measured for the melanoma, ovarian carcinoma, and lymphoma cell lines, respectively, vs. control groups not exposed to the magnetic field. Multicycle flow cytometry revealed that the cell cycle was largely unaltered. Pulsed-field electrophoresis analysis revealed no increase in DNA breaks related to magnetic field exposure. In conclusion, prolonged exposure to a very strong magnetic field appeared to inhibit the growth of threc human tumor cell lines in vitro. The mechanism underlying this effect has not, as yet, been identified, although alteration of cell growth cycle and gross fragmentation of DNA have been excluded as possible contributory factors. Future investigations of this phenomenon may have a significant impact on the future understanding and treatment of cancer. 01996 Wilcy-Liss. Inc.