Abstract
This study investigated the effects of sinusoidal ELF-MF (1 mT; 50 Hz) on the apoptosis induced by four different compounds, namely vinblastine, etoposide, quercetin, and resveratrol, in human K562 chronic myeloid leukemia cells. The exposure to ELF-MF did not affect growth and viability of untreated K562 cells and did not influence the anti-proliferative effects of resveratrol, vinblastine, and etoposide. On the contrary, in quercetin-treated cells, exposure to ELF-MF significantly reduced the percentage of apoptotic cells and the caspase-3 activity and modified the cell cycle profile especially after 48 h of exposure. In addition, the simultaneous treatments for 24 h with quercetin plus ELF-MF increased Bcl-2 protein expression and prevented quercetin-induced downregulation of Mcl-1 and Bcl-xL. Finally, an increase of HSP70 expression was also observed after prolonged ELF-MF treatment. The ELF-MF-dependent modulation of the expression of anti-apoptotic Bcl-2 family and Hsp70 proteins could act as a pro-survival mechanism in K562 cells.
Similar content being viewed by others
References
Vianale G, Reale M, Amerio P, Stefanachi M, Di Luzio S, Muraro R (2008) Extremely low frequency electromagnetic field enhances human keratinocyte cell growth and decreases proinflammatory chemokine production. Br J Dermatol 158:1189–1196
Inhan-Garip A, Akan Z, Oncul Ş, Işal-Turgut I, Tunaya K (2010) Differentiation of K562 cells under ELF-EMF applied at different time courses. Electromagn Biol Med 29:122–130
Sun RG, Chen WF, Qi H, Zhang K, Bu T, Liu Y, Wang SR (2012) Biologic effects of SMF and paclitaxel on K562 human leukemia cells. Gen Physiol Biophys 31:1–10
Iorio R, Bennato F, Mancini F, Colonna R (2013) ELF-MF transiently increases skeletal myoblast migration: possible role of calpain system. Int J Radiat Biol 89:548–561
Zwirska-Korczala K, Jochem J, Adamczyk-Sowa M, Sowa P, Polaniak R, Birkner E, Latocha M, Pilc K, Suchanek R (2005) Effect of extremely low frequency of electromagnetic fields on cell proliferation, antioxidative enzyme activities and lipid peroxidation in 3T3-L1 preadipocytes-an in vitro study. J Physiol Pharmacol 6:101–108
Wolf FI, Torsello A, Tedesco B, Fasanella S, Boninsegna A, D’Ascenzo M, Grassi C, Azzena GB, Cittadini A (2005) 50-Hz extremely low frequency electromagnetic fields enhance cell proliferation and DNA damage: possible involvement of a redox mechanism. Biochim Biophys Acta 1743:120–129
Di Loreto S, Falone S, Caracciolo V, Sebastiani P, D’Alessandro A, Mirabilio A, Zimmitti V, Amicarelli F (2009) Fifty hertz extremely low-frequency magnetic field exposure elicits redox and trophic response in rat-cortical neurons. J Cell Physiol 219:334–343
Iorio R, Delle Monache S, Bennato F, Di Bartolomeo C, Scrimaglio R, Cinque B, Colonna R (2011) Involvement of mitochondrial activity in mediating ELF-EMF stimulatory effect on human sperm motility. Bioelectromagnetics 32:15–27
Piacentini R, Ripoli C, Mezzogori D, Azzena GB, Grassi C (2008) Extremely low-frequency electromagnetic fields promote in vitro neurogenesis via up-regulation of Ca(v)1-channel activity. J Cell Physiol 215:129–139
Thomadaki H, Scolaris A (2006) BCL2 family of apoptosis-related genes: functions and clinical implications in cancer. Crit Rev Clin Lab Sci 43:1–67
Röösli M, Lörtscher M, Egger M, Pfluger D, Schreier N, Lörtscher E, Locher P, Spoerri A, Minder C (2007) Leukemia, brain tumours and exposure to extremely low frequency magnetic fields: Cohort study of Swiss railway employees. Occup Environ Med 64:553–559
Simkó M, Kriehuber R, Weiss DG, Luben RA (1998) Effects of 50 Hz EMF exposure on micronucleus formation and apoptosis in transformed and nontransformed human cell lines. Bioelectromagnetics 19:85–91
Kim J, Ha CS, Lee HJ, Song K (2010) Repetitive exposure to a 60-Hz time-varying magnetic field induces DNA double-strand breaks and apoptosis in human cells. Biochem Biophys Res Commun 400:739–744
Santini MT, Ferrante A, Rainaldi G, Indovina P, Indovina PL (2005) Extremely low frequency (ELF) magnetic fields and apoptosis: a review. Int J Radiat Biol 81:1–11
Inhan-Garip A, Akan Z (2010) Effect of ELF-EMF on number of apoptotic cells; correlation with reactive oxygen species and HSP. Acta Biol Hung 61:158–167
Jian W, Wei Z, Zhiqiang C, Zheng F (2009) X-ray-induced apoptosis of BEL-7402 cell line enhanced by extremely low frequency electromagnetic field in vitro. Bioelectromagnetics 30:163–165
Luukkonen J, Liimatainen A, Höytö A, Juutilainen J, Naarala J (2011) Pre-exposure to 50 Hz magnetic fields modifies menadione-induced genotoxic effects in human SH-SY5Y neuroblastoma cells. PlosOne 6:e18021
Basile A, Zeppa R, Pasquino N, Arra C, Ammirante M, Festa M, Barbieri A, Giudice A, Pascale M, Turco MC, Rosati A (2011) Exposure to 50 Hz electromagnetic field raises the levels of the anti-apoptotic protein BAG3 in melanoma cells. J Cell Physiol 226:2901–2907
Kelly GS (2011) Quercetin. Monograph. Altern Med Rev 16:172–194
Brisdelli F, D’Andrea G, Bozzi A (2009) Resveratrol: a natural polyphenol with multiple chemopreventive properties. Curr Drug Metab 10:530–546
Luzi C, Brisdelli F, Cinque B, Cifone G, Bozzi A (2004) Differential sensitivity to resveratrol-induced apoptosis of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells. Biochem Pharmacol 68:2019–2030
Brisdelli F, Coccia C, Cinque B, Cifone MG, Bozzi A (2007) Induction of apoptosis by quercetin: different response of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells. Mol Cell Biochem 296:137–149
Kirschvink JL (1992) Uniform magnetic fields and double-wrapped coil systems: improved techniques for the design of bioelectromagnetic experiments. Bioelectromagnetics 13:401–411
McGahon AJ, Martin SJ, Bissonnette RP, Mahboubi A, Shi Y, Mogil RJ, Nishioka WK, Green DR (1995) The end of the (cell) line: methods for the study of apoptosis in vitro. Methods Cell Biol 46:153–185
Kohlex C, Orrenius S, Zhivatovsky B (2002) Evaluation of caspase activity in apoptotic cells. J Immunol Methods 265:97–110
LeBel CP, Ishiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive species formation and oxidative stress. Chem Res Toxicol 5:227–231
Tokalov SV, Gutzeit H (2004) Weak electromagnetic fields (50 Hz) elicit a stress response in human cells. Environ Res 94:145–151
Paradisi S, Donelli G, Santini MT, Straface E, Malorni W (1993) A 50-Hz magnetic fields induces structural and biophysical changes in membranes. Bioelectromagnetics 14:247–255
Mannerling A-C, Simkó, Mild KH, Mattsson M-O (2010) Effects of 50-Hz magnetic field exposure on superoxide radical anion formation and HSP70 induction in human K562 cells. Radiat Environ Biophys 49:731–741
Eleuteri AM, Amici M, Bonfili L, Cecarini V, Cuccioloni M, Grimaldi S, Giuliani L, Angeletti M, Fioretti E (2009) 50 Hz extremely low frequency electromagnetic fields enhance protein carbonyl groups content in cancer cells: effects on proteasomal systems. J Biomed Biotechnol 2009:834239
Focke F, Schuermann D, Kuster N, Schär P (2010) DNA fragmentation in human fibroblasts under extremely low frequency electromagnetic field exposure. Mutat Res 683:74–83
Markov MS (2010) Angiogenesis, magnetic fields and ‘window effects’. Cardiology 117:54–56
Vijayababu M, Kanagaraj P, Arunkumar A, Ilangovan R, Aruldhas M, Arunakaran J (2005) Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression. J Cancer Res Clin Oncol 131:765–771
Vidya Priyadarsini R, Senthil Murugan R, Maitreyi S, Ramalingam K, Karunagaran D, Nagini S (2010) The flavonoid quercetin induces cell cycle arrest and mitochondrial-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-kB inhibition. Eur J Pharmacol 649:84–91
Kim W, Bang M, Kim E, Kang N, Jung K, Cho H, Park JH (2005) Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells. J Nutr Biochem 16:155–162
Chen D, Daniel K, Chen M, Kuhn D, Landis-Piwowar K, Dou Q (2005) Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochem Pharmacol 69:1421–1432
Zhang X-M, Chen J, Xia Y-G, Xu Q (2005) Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC-alfa and translocating PKC-delta. Cancer Chemother Pharmacol 55:251–262
Ding G-R, Nakahara T, Tian F-R, Guo Y, Miyakoshi J (2001) Transient suppression of X-ray-induced apoptosis by exposure to power frequency magnetic fields in MCF-7 cells. Biochem Biophys Res Commun 286:953–957
Tian F, Nakahara T, Yoshida M, Honda N, Hirose H, Miyakoshi J (2002) Exposure to power frequency magnetic fields suppresses X-ray-induced apoptosis transiently in Ku80-deficient xrs5 cells. Biochem Biophys Res Commun 292:355–361
Deng X, Gao F, May WS (2003) Bcl2 retards G1/S cell cycle transition by regulating intracellular ROS. Blood 102:3179–3185
Weng C, Li Y, Xu D, Shi Y, Tang H (2005) Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells. J Biol Chem 280:10491–10500
Fanelli C, Coppola S, Barone R, Colussi C, Gualandi G, Volpe P, Ghibelli L (1999) Magnetic fields increase cell survival by inhibiting apoptosis via modulation of Ca2+ influx. FASEB J 13:95–102
Rong Y, Distelhorst CW (2008) Bcl-2 protein family members: versatile regulators of calcium signaling in cell survival and apoptosis. Ann Rev Physiol 70:73–91
De Nicola M, Cordisco S, Cerella C, Albertini MC, D’Alessio M, Accorsi A, Bergamaschi A, Magrini A, Ghibelli L (2006) Magnetic fields protect from apoptosis via redox alteration. Ann NY Acad Sci 1090:59–68
Buldak RJ, Polaniak R, Buldak L, Zwirska-Korczala Ż, Skonieczna M, Monsiol A, Kukla M, Duława-Bułdak A, Birkner E (2012) Short-term exposure to 50 Hz ELF-EMF alters the cisplatin-induced oxidative response in AT478 murine squamous cell carcinoma cells. Bioelectromagnetics 33:641–651
Wei Y, Zhao X, Kariya Y, Fukata H, Teshigawara K, Uchida A (1994) Induction of apoptosis by quercetin: involvement of heat shock protein. Cancer Res 54:4952–4957
Acknowledgments
This work was partially supported by a grant from MIUR (Ministero dell‘Istruzione, dell‘Università e della Ricerca), MURST EX 60 %, to Prof. Argante Bozzi and Dr. Fabrizia Brisdelli.
Conflict of interest
There was no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Brisdelli, F., Bennato, F., Bozzi, A. et al. ELF-MF attenuates quercetin-induced apoptosis in K562 cells through modulating the expression of Bcl-2 family proteins. Mol Cell Biochem 397, 33–43 (2014). https://doi.org/10.1007/s11010-014-2169-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-014-2169-1