Abstract
Ultrasound can induce apoptosis and enhance apoptosis attributable to anticancer drugs, in which cavitation plays the leading role. Cavitation leads to the production of reactive radicals and shear forces, which insult DNA and mitochondria, initiating apoptosis via the cytochrome c–caspase 3 pathway. Cavitation permeabilizes the cell membrane, thereby increasing the intracellular drug level and enhancing the efficacy of the cytotoxic drug. Ultrasonically chemotherapeutic sensitization is effective in both chemosensitive and chemoresistant cancer cells. The biological responses to high-intensity electric pulses are dependent on the voltage applied and the pulse length. Nanosecond electric pulses can pass through plasma and nuclear membranes to create sufficiently high voltages in the cytoplasm and in the nucleus with intact plasma and nuclear membranes, thereby impacting mitochondria or DNA, resulting in apoptosis. Nanosecond electric pulses may induce apoptosis via the intrinsic or the extrinsic pathway, and electrical and mechanical mechanisms may be involved. Both ultrasound and electric pulses can be delivered precisely into preselected tissues, so these two techniques can be developed for targeted cancer therapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abdollahi A, Domhan S, Jenne JW, Hallaj M, Dell’Aqua G, Mueckenthaler M, Richter A, Martin H, Debus J, Ansorge W, Hynynen K, Huber PE (2004) Apoptosis signals in lymphoblasts induced by focused ultrasound. FASEB J 18:1413–1414
Aoi A, Watanabe Y, Mori S, Takahashi M, Vassaux G, Kodama T (2008) Herpes simplex virus thymidine kinase-mediated suicide gene therapy using nano/microbubbles and ultrasound. Ultrasound Med Biol 34:425–434
Ashush H, Rozenszajn LA, Blass M, Barda-Saad M, Azimov D, Radnay J, Zipori D, Rosenschein U (2000) Apoptosis induction of human myeloid leukemic cells by ultrasound exposure. Cancer Res 60:1014–1020
Beebe SJ, Fox PM, Rec LJ, Somers K, Stark RH, Schoenbach KH (2002) Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition. IEEE Trans Plasma Sci 30:286–292
Beebe SJ, Fox PM, Rec LJ, Willis EL, Schoenbach KH (2003) Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells. FASEB J 17:1493–1495
Daigeler A, Chromik AM, Haendschke K, Emmelmann S, Siepmann M, Hensel K, Schmitz G, Klein-Hitpass L, Steinau HU, Lehnhardt M, Hauserz J (2010) Synergistic effects of sonoporation and taurolidin/TRAIL on apoptosis in human pibrosarcoma. Ultrasound Med Biol 36:1893–1906
Danno D, Kanno M, Fujimoto S, Feril LB, Kondo T, Nakamura S (2008) Effects of ultrasound on apoptosis induced by anti-CD20 antibody in CD20-positive B lymphoma cells. Ultrason Sonochem 15:463–471
Dev SB, Rabussay DP, Widera G, Hofmann GA (2000) Medical applications of electroporation. IEEE Trans Plasma Sci 28:206–223
Ermolina I, Polevaya Y, Feldman Y (2001) Study of normal and malignant white blood cells by time domain dielectric spectroscopy. IEEE Trans Dielectr Electr Insul 8:253–261
Escoffre JM, Piron J, Novell A, Bouakaz A (2011) Doxorubicin delivery into tumor cells with ultrasound and microbubbles. Mol Pharm 8:799–806
Feril LB, Kondo T, Zhao QL, Ogawa R (2002) Enhancement of hyperthermia-induced apoptosis by non-thermal effects of ultrasound. Cancer Lett 178:63–70
Feril LB, Kondo T, Zhao QL, Ogawa R, Tachibana K, Kudo N, Fujimoto S, Nakamura S (2003) Enhancement of ultrasound-induced apoptosis and cell lysis by echo-contrast agents. Ultrasound Med Biol 29:331–337
Firestein F, Rozenszajn LA, Shemesh-Darvish L, Elimelech R, Radnay J, Rosenschein U (2003) Induction of apoptosis by ultrasound application in human malignant lymphoid cells: role of mitochondria-caspase pathway activation. Ann N Y Acad Sci 1010:163–166
Ford WE, Ren W, Blackmore PF, Schoenbach KH, Beebe SJ (2010) Nanosecond pulsed electric fields stimulate apoptosis without release of pro-apoptotic factors from mitochondria in B16f10 melanoma. Arch Biochem Biophys 497:82–89
Fry FJ (1993) Intense focused ultrasound in medicine. Some practical guiding physical principles from sound source to focal site in tissue. Eur Urol 23(Suppl 1):2–7
Furusawa Y, Zhao QL, Hassan MA, Tabuchi Y, Takasaki I, Wada S, Kondo T (2010) Ultrasound-induced apoptosis in the presence of Sonazoid and associated alterations in gene expression levels: a possible therapeutic application. Cancer Lett 288:107–115
Furusawa Y, Fujiwara Y, Campbell P, Zhao QL, Ogawa R, Hassan MA, Tabuchi Y, Takasaki I, Takahashi A, Kondo T (2012) DNA double-strand breaks induced by cavitational mechanical effects of ultrasound in cancer cell lines. PLoS One 7:e29012
Girdhani S, Bhosle SM, Thulsidas SA, Kumar A, Mishra KP (2005) Potential of radiosensitizing agents in cancer chemo-radiotherapy. J Can Res Ther 1:129–131
Gowrishankar TR, Esser AT, Vasilkoski Z, Smith KC, Weaver JC (2006) Microdosimetry for conventional and supra-electroporation in cells with organelles. Biochem Biophys Res Commun 341:1266–1276
Hall EH, Schoenbach KH, Beebe SJ (2007) Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null HCT116 colon carcinoma cells. Apoptosis 12:1721–1731
He H, Yu T, Zhang Y (2012) The interaction between a drug and ultrasound in sonochemotherapy against ovarian cancers. Ultraschall Med 33:275–282
Honda H, Kondo T, Zhao QL, Feril LB, Kitagawa H (2004) Role of intracellular calcium ions and reactive oxygen species in apoptosis induced by ultrasound. Ultrasound Med Biol 30:683–692
Hu Q, Viswanadham S, Joshi RP, Schoenbach KH, Beebe SJ, Blackmore PF (2005) Simulations of transient membrane behavior in cells subjected to a high-intensity ultrashort electric pulse. Phys Rev E 71:031914
Isambert H (1998) Understanding the electroporation of cells and artificial bilayer membranes. Phys Rev Lett 80:3404–3407
Jarm T, Cemazar M, Miklavcic D, Sersa G (2010) Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases. Expert Rev Anticancer 10:729–746
Jiang X, Wang X (2004) Cytochrome C-mediated apoptosis. Annu Rev Biochem 73:87–106
Joshi RP, Mishra A, Hu Q, Schoenbach KH, Pakhomov A (2007) Self-consistent analyses for potential conduction block in nerves by an ultrashort high-intensity electric pulse. Phys Rev E 75:061906
Joshi RP, Schoenbach KH (2010) Bioelectric effects of intense ultrashort pulses. Crit Rev Biomed Eng 38:255–304
Kardos N, Luche JL (2001) Sonochemistry of carbohydrate compounds. Carbohydr Res 332:115–131
Kotnik T, Miklavcic D (2006) Theoretical evaluation of voltage inducement on internal membranes of biological cells exposed to electric fields. Biophys J 90:480–491
Lagneaux L, de Meulenaer EC, Delforge A, Dejeneffe M, Massy M, Moerman C, Hannecart B, Canivet Y, Lepeltier MF, Bron D (2002) Ultrasonic low-energy treatment: a novel approach to induce apoptosis in human leukemic cells. Exp Hematol 30:1293–1301
Limtrakul P (2007) Curcumin as chemosensitizer. Adv Exp Med Biol 595:269–300
Lou Y, Zhang Y, He H, Liu Y, Huang P, Yu T (2011) Ultrasound sensitizes chemotherapy in chemoresistant ovarian cancers. Afr J Biotechnol 10:12047–12053
Meiler J, Schuler M (2006) Therapeutic targeting of apoptotic pathways in cancer. Curr Drug Targets 7:1361–1369
Nuccitelli R, Chen X, Pakhomov AG, Baldwin WH, Sheikh S, Pomicter JL, Ren W, Osgood C, Swanson RJ, Kolb JF, Beebe SJ, Schoenbach KH (2009) A new pulsed electric field therapy for melanoma disrupts the tumor’s blood supply and causes complete remission without recurrence. Int J Cancer 125:438–445
Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S (2002) Cytochrome c release from mitochondria proceeds by a two-step process. Proc Natl Acad Sci USA 99:1259–1263
Pakhomov AG, Bowman AM, Ibey BL, Andre FM, Pakhomova ON, Schoenbach KH (2009) Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane. Biochem Biophys Res Commun 385:181–186
Paliwal S, Mitragotri S (2006) Ultrasound-induced cavitation: applications in drug and gene delivery. Expert Opin Drug Deliv 3:713–726
Plati J, Bucur O, Khosravi-Far R (2008) Dysregulation of apoptotic signaling in cancer: molecular mechanisms and therapeutic opportunities. J Cell Biochem 104:1124–1149
Poff JA, Allen CT, Traughber B, Colunga A, Xie J, Chen Z, Wood BJ, Van Waes C, Li KC, Frenkel V (2008) Pulsed high-intensity focused ultrasound enhances apoptosis and growth inhibition of squamous cell carcinoma xenografts with proteasome inhibitor bortezomib. Radiology 248:485–491
Ren W, Beebe SJ (2011) An apoptosis targeted stimulus with nanosecond pulsed electric fields (nsPEFs) in E4 squamous cell carcinoma. Apoptosis 16:382–393
Schoenbach K, Joshi R, Beebe S, Baum C (2009) A scaling law for membrane permeabilization with nanopulses. IEEE Trans Dielectr Electr Insul 16:1224–1235
Schoenbach KH, Hargrave B, Joshi RP, Kolb JF, Nuccitelli R, Osgood C, Pakhomov A, Stacey M, Swanson RJ, White JA, Shu X, Jue Z, Beebe SJ, Blackmore PF, Buescher ES (2007) Bioelectric effects of intense nanosecond pulses. IEEE Trans Dielectr Electr Insul 14:1088–1109
Stride EP, Coussios CC (2010) Cavitation and contrast: the use of bubbles in ultrasound imaging and therapy. Proc Inst Mech Eng Part H 224:171–191
Tabuchi Y, Kondo T, Ogawa R, Mori H (2002) DNA microarray analyses of genes elicited by ultrasound in human U937 cells. Biochem Biophys Res Commun 290:498–503
Tabuchi Y, Ando H, Takasaki I, Feril LB, Zhao QL, Ogawa R, Kudo N, Tachibana K, Kondo T (2007) Identification of genes responsive to low intensity pulsed ultrasound in a human leukemia cell line Molt-4. Cancer Lett 246:149–156
Tang W, Liu Q, Wang X, Wang P, Cao B, Mi N, Zhang J (2008) Involvement of caspase 8 in apoptosis induced by ultrasound-activated hematoporphyrin in sarcoma 180 cells in vitro. J Ultrasound Med 27:645–656
ter Haar G (2007) Therapeutic applications of ultrasound. Prog Biophys Mol Biol 93:111–129
ter Haar G (2001) Acoustic surgery. Phys Today 54:29–34
Vernier PT, Sun Y, Marcu L, Craft CM, Gundersen MA (2004) Nanosecond pulsed electric fields perturb membrane phospholipids in T lymphoblasts. FEBS Lett 572:103–108
Walker K, Pakhomova ON, Kolb J, Schoenbach KS, Stuck BE, Murphy MR, Pakhomov AG (2006) Oxygen enhances lethal effect of high-intensity, ultrashort electrical pulses. Bioelectromagnetics 27:221–225
Wang JJ, Zheng Y, Yang F, Zhao P, Li HF (2010) Survivin small interfering RNA transfected with a microbubble and ultrasound exposure inducing apoptosis in ovarian carcinoma cells. Int J Gynecol Cancer 20:500–506
Watanabe Y, Aoi A, Horie S, Tomita N, Mori S, Morikawa H, Matsumura Y, Vassaux G, Kodama T (2008) Low-intensity ultrasound and microbubbles enhance the antitumor effect of cisplatin. Cancer Sci 99:2525–2531
Wu MH, Zheng XM, Ruan CL, Yang HC, Sun YQ, Wang S, Zhang KD, Liu H (2009) Photoresistances of semi-insulating GaAs photoconductive switch illuminated by 1.064 μ m laser pulse. J Appl Phys 106:023101
Xiang J, Xia X, Jiang Y, Leung AW, Wang X, Xu J, Wang P, Yu H, Bai D, Xu C (2011) Apoptosis of ovarian cancer cells induced by methylene blue-mediated sonodynamic action. Ultrasonics 51:390–395
Yoshida T, Kondo T, Ogawa R, Feril LB, Zhao QL, Watanabe A, Tsukada K (2008) Combination of doxorubicin and low-intensity ultrasound causes a synergistic enhancement in cell killing and an additive enhancement in apoptosis induction in human lymphoma U937 cells. Cancer Chemother Pharmacol 61:559–567
Yu T, Huang X, Hu K, Bai J, Wang Z (2004) Mechanisms of reversal of adriamycin resistance in human ovarian carcinoma cell line by ultrasound. Int J Gynecol Cancer 14:76–81
Yu T, Huang X, Jiang S, Hu K, Kong B, Wang Z (2005a) Ultrastructure alterations in adriamycin-resistant and cisplatin-resistant human ovarian cancer cell lines exposed to nonlethal ultrasound. Int J Gynecol Cancer 15:462–467
Yu T, Xiong Z, Chen S, Tu G (2005b) The use of models in "target" theory to evaluate the survival curves of human ovarian carcinoma cell line exposure to adriamycin combined with ultrasound. Ultrason Sonochem 12:345–348
Yu T, Li S, Zhao J, Mason TJ (2006) Ultrasound: a chemotherapy sensitizer. Technol Cancer Res Treat 5:51–60
Yu T, Zhang Y (2010) Sonochemotherapy against cancers. In: Nowak FM (eds) Sonochemistry: theory, reactions, syntheses, and applications. Nova, Hauppauge, pp 189–200
Yu TH, Huang P (2011) Extracorporeal ultrasound-guided high intensity focused ultrasound therapy: present limitations. Afr J Pharm Pharmacol 5:1501–1507
Yu T, Zhang Y, He H, Zhou S, Liu Y, Huang P (2011) Anticancer potency of cytotoxic drugs after exposure to high-intensity focused ultrasound in the presence of microbubbles and hematoporphyrin. Mol Pharm 8:1408–1415
Acknowledgments
The work in our laboratory was supported by grants from the Natural Science Foundation of China (11174376, 30972830) and the Natural Science Foundation of Chongqing (CSTC 2009BA5049).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Yu, T., Wu, M., Huang, P., Hu, L. (2013). Modulating Apoptosis in Cancer Therapy with Ultrasound and High-Intensity Nanosecond Electric Pulses. In: Resende, R., Ulrich, H. (eds) Trends in Stem Cell Proliferation and Cancer Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6211-4_22
Download citation
DOI: https://doi.org/10.1007/978-94-007-6211-4_22
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-6210-7
Online ISBN: 978-94-007-6211-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)