Abstract
One main issue of thermotherapy is the stress response of mitochondria to heat. Thermotherapies function by inducing lethal heat inside target tissues. Actually spatial and temporal instabilities of temperature distributions inside target volumes require optimized treatment protocols and reliable temperature-control methods during thermotherapies. Since solid tumors present predominant targets to thermotherapy, on the one hand, the hyperthermic stress-induced effects on mitochondrial transmembrane potentials in breast cancer cells (MX1) were analyzed. On the other hand, the intracellular Ca2+ fluctuations in different cell types responding to heat stress were investigated.
Heat sensitivities and stress reactions might be extremely different among different tissue species and tissue dignities; therefore, it is very important to investigate tissue-specific stress responses systematically. Even though this chapter contributes little information, only, to the enlightenment of systemic cellular heat stress mechanisms, it may support the fortification of basic knowledge about systemic stress responses. Using cytoplasmic and intramitochondrial fluorescent Ca2+ probes it was possible to compare hyperthermia-induced changes in the Ca2+ distribution between the cytoplasm and the mitochondria of normal and tumor cells and to examine the relationship between mitochondrial Ca2+ concentration and changes in the viability of these cell types upon hyperthermic treatment. We compared Ca2+ concentrations in cytoplasm and mitochondria in cancerous CX1 and MX1 cells with normal CHO cells after transfer from room temperature (25°C) to 37°C or 43°C. Sudden increase in the incubation temperature (from room temperature to 37°C) induced very different cytoplasmic and mitochondrial Ca2+ fluctuation patterns in normal CHO and CX1 and MX1 tumor cells. Estimating the CX1, MX1, and CHO cell viabilities upon hyperthermic treatment, we found that thermosensitivities increase in the sequence CX1<CHO<MX1. CHO cells were not less sensitive to hyperthermia than were MX1 tumor cells, but results show that the lowest amount of calcium is in the CHO cells, whereas the highest mitochondrial Ca2+ is in the most thermosensitive MX1 cells. The preliminary results are consistent with the conclusion that the sensitivities of cancer cells to hyperthermic treatments depend on the initial mitochondrial Ca2+ concentrations. However, more experiments are needed to confirm these suggestions. Further on, the data presented here might support an optimization of the treatment protocols applied during thermotherapy, particularly LITT and hyperthermia.
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References
B. Gewiese, J. Beuthan, F. Fobbe, D. Stiller, G. Müller, J. Böse-Landgraf, K.J. Wolf, and M. Deimling, Magnetic resonance imaging-controlled laser-induced interstitial thermotherapy, Invest. Radiol. 29(3), 345–351 (1994).
A. Roggan, J.P. Ritz, V. Knappe, C.T. Germer, C. Isbert, D. Schädel, and G. Müller, Radiation planning of thermal laser treatment, Med. Laser Appl. 16(2), 65–72 (2001).
M. Nikfarjam, and C. Christophi, Interstitial laser thermotherapy for liver tumors. Brit. J. Surg. 90(9), 1033–1047 (2003).
J. van der Zee, Heating the patient: a promising approach? Ann. Oncol. 13(8), 1173–1184 (2002).
A. Debes, R. Willers, U. Göbel, and R. Wessalowski, Role of heat treatment in childhood cancers: distinct resistance profiles of solid tumor cell lines towards combined thermotherapy. Pediatr. Blood Cancer 45(5), 663–669 (2004).
T. Hehr, P. Wust, M. Bamberg, and W. Budach, Current and potential role of thermoradiotherapy for solid tumors, Onkologie 26(3), 295–302 (2003).
R. Colombo, A. Salonia, L.F. Da Pozzo, R. Naspro, M. Freschi, R. Paroni, M. Pavone-Malasco, and P. Rigatti, Combination of intravesical chemotherapy and hyperthermia for the treatment of superficial bladder cancers: preliminary and clinical experience. Crit. Rev. Oncol. Hematol. 47(2), 127–139 (2003).
R.B. Campbell, Battling tumors with magnetic nanotherapeutics and hyperthermia: turning up the heat, Nanomedicine 2(5), 649–652 (2007).
M. Johannsen, U. Gneveckow, B. Thiesen, K. Taymoorian, C.H. Cho, N. Waldöfner, R. Scholz, A. Jordan, S. Loening, and P. Wust, Thermotherapy of prostate cancer using magnetic nanoparticles: feasibility, imaging, and three-dimensional temperature distribution. Eur. Urol. 52(6), 1653–1662 (2007).
A. Jordan, R. Scholz, K. Maier-Hauff, F. Landeghem, N. Waldöfner, U. Teichgraeber, J. Pinkernelle, H. Bruhn, F. Neumann, B. Thiesen, A. Deimling, and R. Felix, The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma, J. Neuro-Oncol. 78(1), 7–14 (2006).
J. Gellermann, W. Wlodarczyk, B. Hildebrandt, H. Ganter, A. Nicolau, B. Rau, W. Tilly, H. Fähling, J. Nadobny, R. Felix, and P. Wust, Noninvasive magnetic resonance thermography of recurrent rectal carcinoma in a 1.5 Tesla hybrid system, Cancer Res. 65(13), 5872–5880 (2005).
M. Mack, R. Straub, K. Eichler, O. Söllner, T. Lehnert, and T. Vogl, Breast cancer metastases in liver: laser-induced interstitial thermotherapy-local tumor control rate and survival data. Radiology 233(2), 400–409 (2004).
M.W. Dewhirst, B.L. Viglianti, M. Lora-Michiels, M. Hanson, and P.J. Hoopes, Basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia, Int. J. Hyperthermia 19(3), 267–294 (2003).
H.G. Park, S.L. Han, S.Y. Oh, and H.S. Kang, Cellular responses to mild heat stress. Cell. Mol. Life Sci. 62(1), 10–23 (2005).
D.L. Vaux, Apoptosis and toxicology―what relevance? Toxicology 181–182, 3–7 (2002).
S.Y. Proskuryakov, A.G. Konoplyannikov, and V.L. Gabai, Necrosis: a specific form of programmed cell death? Exp. Cell Res. 283(1), 1–16 (2003).
W.F. Yuuen, K.P. Fung, C.Y. Lee, Y.M. Choy, S.K. Kong, S. Ko, and T.T. Kwok, Hyperthermia and tumor necrosis factor-induced apoptosis via mitochondrial damage, Life Sci. 67(6), 725–732 (2000).
W.F. Ko, K.P. Yuen, C.Y. Fung, Y.M. Lee, H.K. Choy, T.T. Cheng, and S.K. Kwok, Reversal of TNF-a resistance by hyperthermia: role of mitochondria, Life Sci. 67(25), 3113–3121 (2000).
S. Lindquist, The heat-shock response, Annu. Rev. Biochem. 55, 1151–1191 (1986).
L.A. Sonna, J. Fujita, S.L. Gaffin, and C.M. Lilly, Effects of heat and cold stress on mammalian gene expression, J. Appl. Physiol. 92(4), 1725–1742 (2002).
S. Takayama, J.C. Reed, and S. Homma, Heat-shock proteins as regulators of apoptosis. Oncogene 22(56), 9041–9047 (2003).
K.C. Kregel, Molecular biology of thermoregulation: invited review: heat shock proteins: modifying factors in physiological stress responses and acquired thermo tolerance, J. Appl. Physiol. 92(5), 2177–2186 (2002).
K.R.H.W. Funk, F. Nagel, F. Wanka, H.E. Krinke, F. Gölfert, and A. Hofer, Effects of heat shock on the functional morphology of cell organelles observed by video-enhanced microscopy, Anat. Rec. 255(4), 458–64 (1999).
A. Huckriede, A. Heikema, K. Sjollema, P. Briones, and E. Agsteribbe, Morphology of the mitochondria in heat shock protein 60 deficient fibroblasts from mitochondrial myopathy patients. Effects of stress conditions, Virchows Arch. 427(2), 159–65 (1995).
Y.K. Lai, W.C. Lee, C.H. Hu, and G.L. Hammond, The mitochondria are recognition organelles of cell stress, J. Surg. Res. 62(1), 90–94 (1996).
F. Macouillard-Poulletier de Gannes, M. Merle, P. Canioni, and P.J. Voison, Metabolic and cellular characterization of immortalized human microglial cells under heat stress, Neurochem. Int. 33(1), 61–73 (1998).
F. Macouillard-Poulletier de Gannes, N. Leducq, P. Diolez, F. Belloc, M. Merle, P. Canioni, and P.J. Voison, Mitochondrial impairment and recovery after heat shock treatment in a human microglial cell line, Neurochem. Int. 36(3), 233–241 (2000).
S. Jakobs, High resolution imaging of live mitochondria, Biochim. Biophys. Acta 1763(5–6), 561–575 (2006).
E. Carafoli, L. Santella, D. Branca, and M. Brini, Generation, control, and processing of cellular calcium signals, Biochem. Mol. Biol. 36(2), 107–260 (2001).
R. Rafoli, Calcium signaling: a tail for all seasons, Proc. Natl. Acad. Sci. U S A 99, 1115–1122 (2004).
M.J. Erridge, Inositol trisphosphate and calcium signaling, Nature 361, 315–325 (1993).
E.M. Brown, S.M. Quinn, and P.M. Vasseliev, The plasma membrane calcium sensor. In: E. Carafoli and C. Klee (eds.), Calcium as a Cellular Regulator, Oxford University Press, New York, 1999, pp. 295–310.
E. Carafoli, Calcium-mediated cellular signals: a story of failures, Trends Biochem. Sci. 29(7), 371–379 (2004).
L. Santella, and E. Carafoli, Calcium signaling in the cell nucleus, FASEB J. 11(13), 1091–1109 (1997).
N.P. Kinnear, C.N. Wyatt, J.H. Clark, P.J. Calcraft, S. Fleischer, L.H. Jeyakumar, G.F. Nixon, and A.M. Evans, Lysosomes co-localize with ryanodine receptor subtype 3 to form a trigger zone for calcium signalling by NAADP in rat pulmonary arterial smooth muscle, Cell Calcium 44(2), 190–201 (2008).
F. Zhang and P.L. Li, Reconstitution and characterization of a nicotinic acid adenine dinucleotide phosphate (NAADP)-sensitive Ca2+ release channel from liver lysosomes of rats, J. Biol. Chem. 282(35), 25259–25269 (2007).
F. Zhang, G. Zhang, A.Y. Zhang, M.J. Koeberl, E. Wallander, and P.L. Li, Production of NAADP and its role in Ca2+ mobilization associated with lysosomes in coronary arterial myocytes, Am. J. Physiol. Heart Circ. Physiol. 291(1), H274–H282 (2006).
B. Dale, L.J. De Felice, K. Kyozuka, L. Santella, and E. Tosti, Voltage clamp of the nuclear envelope, Proc. R. Soc. Lond. 255, 119–124 (1994).
L. Lanini, O. Bachs, and E. Carafoli, The calcium pump of the liver nuclear membrane is identical to that of endoplasmic reticulum, J. Biol. Chem. 267, 11548–11552 (1992).
L. Antella and K. Kyozuka, Calcium release into the nucleus by 1,4,5-triphosphate and cyclic ADP-ribose gated channels induces the resumption of meiosis in starfish oocytes. Cell Calcium 22, 1–10 (1997).
J.V. Erasimenko, Y. Maruyama, K. Yano, N.J. Dolman, A.V. Tepikin, O.H. Petersen, and O.V. Gerasimenko, NAADP mobilizes Ca2+ from a thapsigargin-sensitive store in the nuclear envelope by activating ryanodine receptors, J. Cell Biol. 163(2), 271–282 (2003).
F. Shibasaki, E.R. Price, and D. Milan, Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4, Nature 382, 370–373 (1996).
R. Rizzuto, M. Brini, M. Murgia, and T. Pozzan, Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighbouring mitochondria, Science 262, 744–747 (1993).
E. Carafoli, The calcium cycle of mitochondria, FEBS Lett. 104, 1–5 (1979).
R. Baniene, Z. Nauciene, S. Maslauskaite, G. Baliutyte, and V. Mildaziene, Contribution of ATP synthase to stimulation of respiration by Ca2+ in heart mitochondria, Syst. Biol. 153(5), 350–3 (2006).
P. Bernardi, Mitochondrial transport of cations: channels, exchangers, and permeability transition, Physiol. Rev. 79, 1127–1155 (1999).
B.A. Bornstein, P.S. Zouranjian, J.L. Hansen, S.M. Fraser, L.A. Gelwan, B.B.A. Teichler, and G.K. Svensson, Local hyperthermia, radiation therapy, and chemotherapy in patients with local-regional recurrence of breast carcinoma, Int. J. Radiat. Oncol. Biol. Phys. 25, 79–85 (1992).
S. Ringer, A further contribution regarding the influence of different constituents of the blood on the contraction of the heart, J. Physiol. 4, 29–43 (1883).
P.M. Hopkins, Malignant hyperthermia: advances in clinical management and diagnosis. Br. J. Anaesth. 85, 118–28 (2002).
N. Sambuughin, Y. Sei, K.L. Gallagher, H.W. Wyre, D. Madsen, T.E. Nelson, J.E. Fletcher, H. Rosenberg, and S.M. Muldoon, North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations, Anasthesiologie 95, 594–599 (2001).
F.K. Storm, Background, principles and practice. In: F.K. Storm (ed.), Hyperthermia in Cancer Therapy, GK Hall Medical Publishers, Boston, 1986, pp. 1–8.
N.R. Datta, A.K. Bose, H.K. Kapoor, and S. Gupta, Head and neck cancers: results of thermoradiotherapy versus radiotherapy. Int. J. Hyperthermia 6(3), 479–486 (1990).
W.F. Yuen, K.P. Fung, C.Y. Lee, Y.M. Choy, S.K. Kong, S. Ko, and T.T. Kwok, Hyperthermia and tumor necrosis factor-induced apoptosis via mitochondrial damage, Life Sci. 67(6), 725–732 (2000).
S. Ko, W.F. Yuen, K.P. Fung, C.Y. Lee, Y.M. Choy, H.K. Cheng, T.T. Kwok, and S.K. Kong, Reversal of TNF-resistance by hyperthermia role of mitochondria, Life Sci. 67(25), 3113–3121 (2000).
L. Qian, X. Song, H. Ren, J. Gong, and S. Cheng, Mitochondrial mechanism of heat stress-induced injury in rat cardiomyocyte, Cell Stress Chaperones 9(3), 281–293 (2004).
S.H.P. Chan, and R.L. Barbour, Adenine nucleotide transport in hepatoma mitochondria. Characterisation of factors influencing the kinetics of ATP/ADP uptake, Biochim. Biophys. Acta 723, 104–113 (1983).
S.K. Calderwood, M.A. Stevenson, and G.M. Hahn, Effects of heat on cell calcium and inositol lipid metabolism, Radiat. Res. 113(3), 414–425 (1988).
Y. Itagaki, K. Akagi, M. Uda, and Y. Tanaka, Role of intracellular calcium concentration on tumor cell death from hyperthermia, Oncol. Rep. 5(1), 139–141 (1998).
K. Kameda, T. Kondo, K. Tanabe, Q.L. Zhao, and H. Seto, The role of intracellular Ca(2+) in apoptosis induced by hyperthermia and its enhancement by verapamil in U937 cells, Int. J. Radiat. Oncol. Biol. Phys. 49(5), 1369–1379 (2001).
C.A. Vidair, and W.C. Dewey, Evaluation of a role for intracellular Na+, K+, Ca2+, and Mg2+ in hyperthermic cell killing, Radiat. Res. 105(2), 187–200 (1986).
J.R. Dynlacht, W.C. Hyun, and W.C. Dewey, Changes in intracellular free calcium during hyperthermia: effects of local anesthetics and induction of thermotolerance, cytometry 14(2), 223–229 (1993).
P.K. Wierenga, G.J. Stege, H.H. Kampinga, and A.W. Konings, Intracellular free calcium concentrations in cell suspensions during hyperthermia, Eur. J. Cell. Biol. 63(1), 68–76 (1994).
E.D. Wieder, and M.H. Fox, The role of intracellular free calcium in the cellular response to hyperthermia, Int. J. Hyperthermia 11(5), 733–742 (1995).
http://www.biosource.com/content/literatureContent/PDFs/alamarbluebooklet.pdf
http://probes.invitrogen.com/servlets/spectra?fileid=3168p82
http://probes.invitrogen.com/servlets/spectra?fileid=3168p82
http://probes.invitrogen.com/servlets/spectra?fileid=7514moh
S.L. Keeling, Total variation based convex filters for medical imaging, Appl. Math. Comput. 139(1), 101–109 (2003).
J.L. Wang, D.S. Ke, and M.T. Lin, Heat shock pretreatment may protect against heatstroke-induced circulatory shock and cerebral ischemia by reducing oxidative stress and energy depletion, Shock 23(2), 161–167 (2005).
C. Dressler, O. Minet, V. Novkov, G. Müller, and J. Beuthan, Microscopical heat stress investigations under application of quantum dots, J. Biomed. Opt. 10(4), 1–9 (2005).
J. Beuthan, C. Dressler, and O. Minet, Laser induced fluorescence detection of quantum dots redistributed in thermally stressed tumor cells, Laser Phys. 14(2), 213–219 (2004).
P. Keshavan, S.J. Schwemberger, D.L.H. Smith, G.F. Babcock, and S.D. Zucker, Unconjugated bilirubin induces apoptosis in colon cancer cells by triggering mitochondrial depolarization, Int. J. Cancer 112(3), 433–445 (2004).
M. Crompton, The mitochondrial permeability transition pore and its role in cell death, Biochem. J. 341(2), 233–249 (1999).
J.S. Kim, L. He, and J.L. Lemasters, Mitochondrial permeability transition: a common pathway to necrosis and apoptosis, Biochem. Biophys. Res. Commun. 304(3), 463–470 (2003).
A. Cossarizza, M. Baccarani-Contri, G. Kalashnikova, and C. Francheschi, A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5ʹ,6,6ʹ-tetrachloro-1,1ʹ,3,3ʹ-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochem. Biophys. Res. Commun. 197(1), 40–45 (1993).
S.J. Zunino, and D.H. Storms, Resveratrol-induced apoptosis is enhanced in acute lymphoblastic leukemia cells by modulation of the mitochondrial permeability transition pore. Cancer Lett. 240(1), 123–134 (2006).
C.J. Lieven, J.P. Vrabec, and L.A. Levin, The effects of oxidative stress on mitochondrial transmembrane potential in retinal ganglion cells. Antioxid. Redox Signal. 5(5), 641–646 (2003).
M.R. Duchen, A. Leyssens, and M. Crompton, Transient mitochondrial depolarizations reflect focal sarcoplasmic reticular calcium release in single cardiomyocytes. J. Cell Biol. 142(4), 975–988 (1998).
D.E. Clapham, Calcium Signal. Cell 131, 1047–1058 (2007).
C. Dressler, J. Beuthan, G. Müller, U. Zabarylo, and O. Minet, Fluorescence imaging of heat-stress induced mitochondrial long-term depolarization in breast cancer cells, J. Fluor. 16(5), 689–695 (2006).
C.M. O´Reilly, K.E. Fogarty, R.M. Drummond, R.A. Tuft, and J.V. Walsh Jr., Quantitative analysis of spontaneous mitochondrial depolarizations, Biophys. J. 85(5), 3350–3357 (2003).
P. Bernardi, L. Scorrano, R. Colonna, V. Petronelli, and F. Di Lisa, Mitochondria and cell death, Eur. J. Biochem. 264(3), 687–701 (1999).
J.C. Bischof, J. Padanilam, W.H. Holmes, R.M. Ezzell, and R.C. Lee, Dynamics of cell membrane permeability changes at supraphysiological temperatures, Biophys. J. 68(6), 2608–2614 (1995).
M.A. Stevenson, S.K. Calderwood, and G.M. Hahn, Effect of hyperthermia (45°C) on calcium flux in Chinese hamster ovary HA-1 fibroblasts and its potential role in cytotoxicity and heat resistance, Cancer Res. 47(14), 3712–7 (1987).
J.D. Schertzer, H.J. Green, and A.R. Tupling, Thermal instability of rat muscle sarcoplasmic reticulum Ca2+-ATPase function. Am. J. Physiol. Endocrinol. Metab. 283(4), 722–728 (2002).
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Minet, O., Dressler, C., Beuthan, J., Zabaryło, U., Zukiene, R., Midaziene, V. (2010). Fluorescence Imaging of Calcium Loading and Mitochondrial Depolarization in Cancer Cells Exposed to Heat Stress. In: Geddes, C.D. (eds) Reviews in Fluorescence 2008. Reviews in Fluorescence 2008, vol 2008. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1260-2_4
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