Skip to main content

Advertisement

SpringerLink
Log in

Induction of reactive oxygen species: an emerging approach for cancer therapy

  • Review
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Reactive oxygen species (ROS), a group of ions and molecules, include hydroxyl radicals (·OH), alkoxyl radicals, superoxide anion (O2·−), singlet oxygen (1O2) and hydrogen peroxide (H2O2). Hydroxyl radicals and alkoxyl radicals are extremely and highly reactive species respectively. Endogenous ROS are mainly formed in mitochondrial respiratory chain. Low levels of ROS play important roles in regulating biological functions in mammalian cells. However, excess production of ROS can induce cell death by oxidative damaging effects to intracellular biomacromolecules. Cancer cell death types induced by ROS include apoptotic, autophagic, ferroptotic and necrotic cell death. Since abnormal metabolism in cancer cells, they have higher ROS content compared to normal cells. The higher endogenous ROS levels in cancer cells endow them more susceptible to the ROS-induction treatment. Indeed, some anticancer drugs currently used in clinic, such as molecular targeted drugs and chemotherapeutic agents, effectively kill cancer cells by inducing ROS generation. In addition, photodynamic therapy (PDT) is mainly based on induction of ROS burst to kill cancer cells. The mechanism of cell death induced by radiotherapy using ionizing radiation also refers to ROS production. Moreover, ROS play an important role in tumor immune therapy. Altogether, combining above traditional treatments with ROS-induced agents will be considered as a promising strategy in cancer therapy. In this review, we focus on our current understanding of the anticancer effects of ROS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8:579–591

    Article  CAS  PubMed  Google Scholar 

  2. Idelchik M, Begley U, Begley TJ, Melendez JA (2017) Mitochondrial ROS control of cancer. Semin Cancer Biol. doi:10.1016/S1044-579X(17)30098-6

  3. Hendrick E, Peixoto P, Blomme A, Polese C, Matheus N, Cimino J et al (2017) Metabolic inhibitors accentuate the anti-tumoral effect of HDAC5 inhibition. Oncogene 36:4859–4874

  4. Chen P, Luo X, Nie P, Wu B, Xu W, Shi X et al (2017) CQ synergistically sensitizes human colorectal cancer cells to SN-38/CPT-11 through lysosomal and mitochondrial apoptotic pathway via p53-ROS cross-talk. Free Radic Biol Med 104:280–297

    Article  CAS  PubMed  Google Scholar 

  5. Scialo F, Mallikarjun V, Stefanatos R, Sanz A (2013) Regulation of lifespan by the mitochondrial electron transport chain: reactive oxygen species-dependent and reactive oxygen species-independent mechanisms. Antioxid Redox Signal 19:1953–1969

    Article  CAS  PubMed  Google Scholar 

  6. Raj L, Ide T, Gurkar AU, Foley M, Schenone M, Li X et al (2011) Selective killing of cancer cells by a small molecule targeting the stress response to ROS. Nature 475:231–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Trachootham D, Zhang H, Zhang W, Feng L, Du M, Zhou Y et al (2008) Effective elimination of fludarabine-resistant CLL cells by PEITC through a redox-mediated mechanism. Blood 112:1912–1922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chio I, Tuveson DA (2017) ROS in cancer: the burning question. Trends Mol Med 23:411–429

    Article  CAS  PubMed  Google Scholar 

  9. Nakamura S, Nakanishi A, Takazawa M, Okihiro S, Urano S, Fukui K (2016) Ionomycin-induced calcium influx induces neurite degeneration in mouse neuroblastoma cells: analysis of a time-lapse live cell imaging system. Free Radic Res 50:1214–1225

    Article  CAS  PubMed  Google Scholar 

  10. Zou ZZ, Nie PP, Li YW, Hou BX, Rui-Li, Shi XP et al (2017) Synergistic induction of apoptosis by salinomycin and gefitinib through lysosomal and mitochondrial dependent pathway overcomes gefitinib resistance in colorectal cancer. Oncotarget 8:22414–22432

    PubMed  Google Scholar 

  11. Dickinson BC, Chang CJ (2011) Chemistry and biology of reactive oxygen species in signaling or stress responses. Nat Chem Biol 7:504–511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sumimoto H (2008) Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species. FEBS J 275:3249–3277

    Article  CAS  PubMed  Google Scholar 

  13. Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24:R453-R462

    Article  PubMed Central  CAS  Google Scholar 

  14. Jeon SM, Chandel NS, Hay N (2012) AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 485:661–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Luo X, Yao J, Nie P, Yang Z, Feng H, Chen P et al (2016) FOXM1 promotes invasion and migration of colorectal cancer cells partially dependent on HSPA5 transactivation. Oncotarget 7:26480–26495

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zhang S, Zhao BS, Zhou A, Lin K, Zheng S, Lu Z et al (2017) m6A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell 31:591–606

    Article  CAS  PubMed  Google Scholar 

  17. Park HJ, Carr JR, Wang Z, Nogueira V, Hay N, Tyner AL et al (2009) FoxM1, a critical regulator of oxidative stress during oncogenesis. EMBO J 28:2908–2918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liou GY, Doppler H, DelGiorno KE, Zhang L, Leitges M, Crawford HC et al (2016) Mutant KRas-induced mitochondrial oxidative stress in acinar cells upregulates EGFR signaling to drive formation of pancreatic precancerous lesions. Cell Rep 14:2325–2336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tobiume K, Matsuzawa A, Takahashi T, Nishitoh H, Morita K, Takeda K et al (2001) ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis. EMBO Rep 2:222–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Dhanasekaran DN, Reddy EP (2008) JNK signaling in apoptosis. Oncogene 27:6245–6251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhang J, Wang X, Vikash V, Ye Q, Wu D, Liu Y et al (2016) ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev 2016:4350965

    PubMed  PubMed Central  Google Scholar 

  23. Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH et al (2010) ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci USA 107:4153–4158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Potter CJ, Pedraza LG, Xu T (2002) Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol 4:658–665

    Article  CAS  PubMed  Google Scholar 

  25. Ishaq M, Kumar S, Varinli H, Han ZJ, Rider AE, Evans MD et al (2014) Atmospheric gas plasma-induced ROS production activates TNF-ASK1 pathway for the induction of melanoma cancer cell apoptosis. Mol Biol Cell 25:1523–1531

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Nadeau PJ, Charette SJ, Landry J (2009) REDOX reaction at ASK1-Cys250 is essential for activation of JNK and induction of apoptosis. Mol Biol Cell 20:3628–3637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kim S, Lee TJ, Leem J, Choi KS, Park JW, Kwon TK (2008) Sanguinarine-induced apoptosis: generation of ROS, down-regulation of Bcl-2, c-FLIP, and synergy with TRAIL. J Cell Biochem 104:895–907

    Article  CAS  PubMed  Google Scholar 

  28. Wang L, Azad N, Kongkaneramit L, Chen F, Lu Y, Jiang BH et al (2008) The Fas death signaling pathway connecting reactive oxygen species generation and FLICE inhibitory protein down-regulation. J Immunol 180:3072–3080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Devadas S, Zaritskaya L, Rhee SG, Oberley L, Williams MS (2002) Discrete generation of superoxide and hydrogen peroxide by T cell receptor stimulation: selective regulation of mitogen-activated protein kinase activation and fas ligand expression. J Exp Med 195:59–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gulow K, Kaminski M, Darvas K, Suss D, Li-Weber M, Krammer PH (2005) HIV-1 trans-activator of transcription substitutes for oxidative signaling in activation-induced T cell death. J Immunol 174:5249–5260

    Article  PubMed  Google Scholar 

  31. Jin X, Song L, Liu X, Chen M, Li Z, Cheng L et al (2014) Protective efficacy of vitamins C and E on p,p’-DDT-induced cytotoxicity via the ROS-mediated mitochondrial pathway and NF-kappaB/FasL pathway. PLoS ONE 9:e113257

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Faris M, Latinis KM, Kempiak SJ, Koretzky GA, Nel A (1998) Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter. Mol Cell Biol 18:5414–5424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu Y, Borchert GL, Surazynski A, Hu CA, Phang JM (2006) Proline oxidase activates both intrinsic and extrinsic pathways for apoptosis: the role of ROS/superoxides, NFAT and MEK/ERK signaling. Oncogene 25:5640–5647

    Article  CAS  PubMed  Google Scholar 

  34. Dewangan J, Tandon D, Srivastava S, Verma AK, Yapuri A, Rath SK (2017) Novel combination of salinomycin and resveratrol synergistically enhances the anti-proliferative and pro-apoptotic effects on human breast cancer cells. Apoptosis. doi:10.1007/s10495-017-1394-y

  35. Madesh M, Hajnoczky G (2001) VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release. J Cell Biol 155:1003–1015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Queiroga CS, Almeida AS, Martel C, Brenner C, Alves PM, Vieira HL (2010) Glutathionylation of adenine nucleotide translocase induced by carbon monoxide prevents mitochondrial membrane permeabilization and apoptosis. J Biol Chem 285:17077–17088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zuo Y, Xiang B, Yang J, Sun X, Wang Y, Cang H et al (2009) Oxidative modification of caspase-9 facilitates its activation via disulfide-mediated interaction with Apaf-1. Cell Res 19:449–457

    Article  CAS  PubMed  Google Scholar 

  38. Katoh I, Tomimori Y, Ikawa Y, Kurata S (2004) Dimerization and processing of procaspase-9 by redox stress in mitochondria. J Biol Chem 279:15515–15523

    Article  CAS  PubMed  Google Scholar 

  39. Luanpitpong S, Chanvorachote P, Stehlik C, Tse W, Callery PS, Wang L et al (2013) Regulation of apoptosis by Bcl-2 cysteine oxidation in human lung epithelial cells. Mol Biol Cell 24:858–869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Li D, Ueta E, Kimura T, Yamamoto T, Osaki T (2004) Reactive oxygen species (ROS) control the expression of Bcl-2 family proteins by regulating their phosphorylation and ubiquitination. Cancer Sci 95:644–650

    Article  CAS  PubMed  Google Scholar 

  41. Luanpitpong S, Chanvorachote P, Nimmannit U, Leonard SS, Stehlik C, Wang L et al (2012) Mitochondrial superoxide mediates doxorubicin-induced keratinocyte apoptosis through oxidative modification of ERK and Bcl-2 ubiquitination. Biochem Pharmacol 83:1643–1654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zou Z, Yuan Z, Zhang Q, Long Z, Chen J, Tang Z et al (2012) Aurora kinase A inhibition-induced autophagy triggers drug resistance in breast cancer cells. Autophagy 8:1798–1810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhao Y, Qu T, Wang P, Li X, Qiang J, Xia Z et al (2016) Unravelling the relationship between macroautophagy and mitochondrial ROS in cancer therapy. Apoptosis 21:517–531

    Article  CAS  PubMed  Google Scholar 

  44. Chen Y, McMillan-Ward E, Kong J, Israels SJ, Gibson SB (2008) Oxidative stress induces autophagic cell death independent of apoptosis in transformed and cancer cells. Cell Death Differ 15:171–182

    Article  CAS  PubMed  Google Scholar 

  45. Tripathi DN, Zhang J, Jing J, Dere R, Walker CL (2016) A new role for ATM in selective autophagy of peroxisomes (pexophagy). Autophagy 12:711–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Byun YJ, Kim SK, Kim YM, Chae GT, Jeong SW, Lee SB (2009) Hydrogen peroxide induces autophagic cell death in C6 glioma cells via BNIP3-mediated suppression of the mTOR pathway. Neurosci Lett 461:131–135

    Article  CAS  PubMed  Google Scholar 

  47. Pallichankandy S, Rahman A, Thayyullathil F, Galadari S (2015) ROS-dependent activation of autophagy is a critical mechanism for the induction of anti-glioma effect of sanguinarine. Free Radic Biol Med 89:708–720

    Article  CAS  PubMed  Google Scholar 

  48. Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 26:1749–1760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Song C, Mitter SK, Qi X, Beli E, Rao HV, Ding J et al (2017) Oxidative stress-mediated NFkappaB phosphorylation upregulates p62/SQSTM1 and promotes retinal pigmented epithelial cell survival through increased autophagy. PLoS ONE 12:e171940

    Google Scholar 

  50. Zhang Y, Su SS, Zhao S, Yang Z, Zhong CQ, Chen X et al (2017) RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nat Commun 8:14329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sun W, Wu X, Gao H, Yu J, Zhao W, Lu JJ et al (2017) Cytosolic calcium mediates RIP1/RIP3 complex-dependent necroptosis through JNK activation and mitochondrial ROS production in human colon cancer cells. Free Radic Biol Med 108:433–444

    Article  CAS  PubMed  Google Scholar 

  52. Zhou Z, Lu B, Wang C, Wang Z, Luo T, Piao M et al (2017) RIP1 and RIP3 contribute to shikonin-induced DNA double-strand breaks in glioma cells via increase of intracellular reactive oxygen species. Cancer Lett 390:77–90

    Article  PubMed  CAS  Google Scholar 

  53. Chauhan AK, Min KJ, Kwon TK (2017) RIP1-dependent reactive oxygen species production executes artesunate-induced cell death in renal carcinoma Caki cells. Mol Cell Biochem. doi:10.1007/s11010-017-3052-7

  54. Dixon SJ, Stockwell BR (2014) The role of iron and reactive oxygen species in cell death. Nat Chem Biol 10:9–17

    Article  CAS  PubMed  Google Scholar 

  55. Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC et al (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325:332–336

    Article  CAS  PubMed  Google Scholar 

  56. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:1060–1072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Viswanathan VS, Ryan MJ, Dhruv HD, Gill S, Eichhoff OM, Seashore-Ludlow B et al (2017) Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature 547:453–457

  58. Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS et al (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156:317–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gao M, Monian P, Quadri N, Ramasamy R, Jiang X (2015) Glutaminolysis and transferrin regulate ferroptosis. Mol Cell 59:298–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Liu L, Wei Y, Zhai S, Chen Q, Xing D (2015) Dihydroartemisinin and transferrin dual-dressed nano-graphene oxide for a pH-triggered chemotherapy. Biomaterials 62:35–46

    Article  CAS  PubMed  Google Scholar 

  61. Roh JL, Kim EH, Jang H, Shin D (2017) Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis. Redox Biol 11:254–262

    Article  CAS  PubMed  Google Scholar 

  62. Mi YJ, Geng GJ, Zou ZZ, Gao J, Luo XY, Liu Y et al (2015) Dihydroartemisinin inhibits glucose uptake and cooperates with glycolysis inhibitor to induce apoptosis in non-small cell lung carcinoma cells. PLoS ONE 10:e120426

    Google Scholar 

  63. Hamai A, Caneque T, Muller S, Mai TT, Hienzsch A, Ginestier C et al (2017) An iron hand over cancer stem cells. Autophagy 13:1465–1466

  64. Guo J, Xu B, Han Q, Zhou H, Xia Y, Gong C et al (2017) Ferroptosis: a novel anti-tumor action for cisplatin. Cancer Res Treat. doi:10.4143/crt.2016.572

  65. Yang Y, Guo R, Tian X, Zhang Z, Zhang P, Li C et al (2017) Synergistic anti-tumor activity of Nimotuzumab in combination with Trastuzumab in HER2-positive breast cancer. Biochem Biophys Res Commun 489:523–527

    Article  CAS  PubMed  Google Scholar 

  66. Santoro V, Jia R, Thompson H, Nijhuis A, Jeffery R, Kiakos K et al (2016) Role of reactive oxygen species in the abrogation of oxaliplatin activity by cetuximab in colorectal cancer. J Natl Cancer Inst 108:v394

    Article  Google Scholar 

  67. Cao S, Xia M, Mao Y, Zhang Q, Donkor PO, Qiu F et al (2016) Combined oridonin with cetuximab treatment shows synergistic anticancer effects on laryngeal squamous cell carcinoma: involvement of inhibition of EGFR and activation of reactive oxygen species-mediated JNK pathway. Int J Oncol 49:2075–2087

    Article  PubMed  Google Scholar 

  68. Fack F, Espedal H, Keunen O, Golebiewska A, Obad N, Harter PN et al (2015) Bevacizumab treatment induces metabolic adaptation toward anaerobic metabolism in glioblastomas. Acta Neuropathol 129:115–131

    Article  CAS  PubMed  Google Scholar 

  69. Guo XL, Li D, Sun K, Wang J, Liu Y, Song JR et al (2013) Inhibition of autophagy enhances anticancer effects of bevacizumab in hepatocarcinoma. J Mol Med (Berl) 91:473–483

    Article  CAS  Google Scholar 

  70. Gautam J, Ku JM, Regmi SC, Jeong H, Wang Y, Banskota S et al (2017) Dual inhibition of NOX2 and receptor tyrosine kinase by BJ-1301 enhances anticancer therapy efficacy via suppression of autocrine stimulatory factors in lung cancer. Mol Cancer Ther. doi:10.1158/1535-7163

  71. Abdel-Aziz AK, Shouman S, El-Demerdash E, Elgendy M, Abdel-Naim AB (2014) Chloroquine synergizes sunitinib cytotoxicity via modulating autophagic, apoptotic and angiogenic machineries. Chem Biol Interact 217:28–40

    Article  CAS  PubMed  Google Scholar 

  72. Leone A, Roca MS, Ciardiello C, Terranova-Barberio M, Vitagliano C, Ciliberto G et al (2015) Vorinostat synergizes with EGFR inhibitors in NSCLC cells by increasing ROS via up-regulation of the major mitochondrial porin VDAC1 and modulation of the c-Myc-NRF2-KEAP1 pathway. Free Radic Biol Med 89:287–299

    Article  CAS  PubMed  Google Scholar 

  73. Okon IS, Coughlan KA, Zhang M, Wang Q, Zou MH (2015) Gefitinib-mediated reactive oxygen specie (ROS) instigates mitochondrial dysfunction and drug resistance in lung cancer cells. J Biol Chem 290:9101–9110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Shan F, Shao Z, Jiang S, Cheng Z (2016) Erlotinib induces the human non-small-cell lung cancer cells apoptosis via activating ROS-dependent JNK pathways. Cancer Med 5:3166–3175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Orcutt KP, Parsons AD, Sibenaller ZA, Scarbrough PM, Zhu Y, Sobhakumari A et al (2011) Erlotinib-mediated inhibition of EGFR signaling induces metabolic oxidative stress through NOX4. Cancer Res 71:3932–3940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Nie P, Hu W, Zhang T, Yang Y, Hou B, Zou Z (2015) Synergistic induction of Erlotinib-mediated apoptosis by resveratrol in human non-small-cell lung cancer cells by down-regulating survivin and up-regulating PUMA. Cell Physiol Biochem 35:2255–2271

    Article  CAS  PubMed  Google Scholar 

  77. Wardman P (2007) Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: progress, pitfalls, and prospects. Free Radic Biol Med 43:995–1022

    Article  CAS  PubMed  Google Scholar 

  78. Bonini MG, Siraki AG, Atanassov BS, Mason RP (2007) Immunolocalization of hypochlorite-induced, catalase-bound free radical formation in mouse hepatocytes. Free Radic Biol Med 42:530–540

    Article  CAS  PubMed  Google Scholar 

  79. Hui KF, Lam BH, Ho DN, Tsao SW, Chiang AK (2013) Bortezomib and SAHA synergistically induce ROS-driven caspase-dependent apoptosis of nasopharyngeal carcinoma and block replication of Epstein-Barr virus. Mol Cancer Ther 12:747–758

    Article  CAS  PubMed  Google Scholar 

  80. Yin L, Kufe T, Avigan D, Kufe D (2014) Targeting MUC1-C is synergistic with bortezomib in downregulating TIGAR and inducing ROS-mediated myeloma cell death. Blood 123:2997–3006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Xian M, Cao H, Cao J, Shao X, Zhu D, Zhang N et al (2017) Bortezomib sensitizes human osteosarcoma cells to adriamycin-induced apoptosis through ROS-dependent activation of p-eIF2alpha/ATF4/CHOP axis. Int J Cancer 141:1029–1041

    Article  CAS  PubMed  Google Scholar 

  82. Fan WH, Hou Y, Meng FK, Wang XF, Luo YN, Ge PF (2011) Proteasome inhibitor MG-132 induces C6 glioma cell apoptosis via oxidative stress. Acta Pharmacol Sin 32:619–625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Park S, Park JA, Yoo H, Park HB, Lee Y (2017) Proteasome inhibitor-induced cleavage of HSP90 is mediated by ROS generation and caspase 10-activation in human leukemic cells. Redox Biol 13:470–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Bhalla S, Balasubramanian S, David K, Sirisawad M, Buggy J, Mauro L et al (2009) PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-kappaB mechanisms and is synergistic with bortezomib in lymphoma cells. Clin Cancer Res 15:3354–3365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Sholler GS, Currier EA, Dutta A, Slavik MA, Illenye SA, Mendonca MC et al (2013) PCI-24781 (abexinostat), a novel histone deacetylase inhibitor, induces reactive oxygen species-dependent apoptosis and is synergistic with bortezomib in neuroblastoma. J Cancer Ther Res 2:21

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Cornago M, Garcia-Alberich C, Blasco-Angulo N, Vall-Llaura N, Nager M, Herreros J et al (2014) Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe. Cell Death Dis 5:e1435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Karthik S, Sankar R, Varunkumar K, Anusha C, Ravikumar V (2015) Blocking NF-kappaB sensitizes non-small cell lung cancer cells to histone deacetylase inhibitor induced extrinsic apoptosis through generation of reactive oxygen species. Biomed Pharmacother 69:337–344

    Article  CAS  PubMed  Google Scholar 

  88. Hedrick E, Crose L, Linardic CM, Safe S (2015) Histone deacetylase inhibitors inhibit rhabdomyosarcoma by reactive oxygen species-dependent targeting of specificity protein transcription factors. Mol Cancer Ther 14:2143–2153

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Miao Z, Yu F, Ren Y, Yang J (2017) d, l-Sulforaphane induces ROS-dependent apoptosis in human gliomablastoma cells by inactivating STAT3 signaling pathway. Int J Mol Sci 18

  90. Hu Y, Zhao C, Zheng H, Lu K, Shi D, Liu Z et al (2017) A novel STAT3 inhibitor HO-3867 induces cell apoptosis by reactive oxygen species-dependent endoplasmic reticulum stress in human pancreatic cancer cells. Anticancer Drugs 28:392–400

    Article  CAS  PubMed  Google Scholar 

  91. Shackelford DB, Shaw RJ (2009) The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer 9:563–575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Wu S, Xing D (2012) Mechanism of mitochondrial membrane permeabilization during apoptosis under photofrin-mediated photodynamic therapy. J Xray Sci Technol 20:363–372

    CAS  PubMed  Google Scholar 

  93. van Straten D, Mashayekhi V, de Bruijn HS, Oliveira S, Robinson DJ (2017) Oncologic photodynamic therapy: basic principles, current clinical status and future directions. Cancers (Basel) 9(2):E19

    Article  Google Scholar 

  94. Gdovin MJ, Kadri N, Rios L, Holliday S, Jordan Z (2017) Focal photodynamic intracellular acidification as a cancer therapeutic. Semin Cancer Biol 43:147–156

    Article  CAS  PubMed  Google Scholar 

  95. Garg AD, Dudek AM, Ferreira GB, Verfaillie T, Vandenabeele P, Krysko DV et al (2013) ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death. Autophagy 9:1292–1307

    Article  CAS  PubMed  Google Scholar 

  96. Wei Y, Song J, Chen Q, Xing D (2012) Enhancement of photodynamic antitumor effect with pro-oxidant ascorbate. Lasers Surg Med 44:69–75

    Article  PubMed  Google Scholar 

  97. McHale AP, Callan JF, Nomikou N, Fowley C, Callan B (2016) Sonodynamic therapy: concept, mechanism and application to cancer treatment. Adv Exp Med Biol 880:429–450

    Article  CAS  PubMed  Google Scholar 

  98. Trendowski M (2014) The promise of sonodynamic therapy. Cancer Metastasis Rev 33:143–160

    Article  CAS  PubMed  Google Scholar 

  99. Misik V, Riesz P (2000) Free radical intermediates in sonodynamic therapy. Ann N Y Acad Sci 899:335–348

    Article  CAS  PubMed  Google Scholar 

  100. Trendowski M (2015) Using the promise of sonodynamic therapy in the clinical setting against disseminated cancers. Chemother Res Pract 2015:316015

    PubMed  PubMed Central  Google Scholar 

  101. Chen H, Gao W, Yang Y, Guo S, Wang H, Wang W et al (2014) Inhibition of VDAC1 prevents Ca(2)(+)-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages. Apoptosis 19:1712–1726

    Article  CAS  PubMed  Google Scholar 

  102. Wang H, Yang Y, Chen H, Dan J, Cheng J, Guo S et al (2014) The predominant pathway of apoptosis in THP-1 macrophage-derived foam cells induced by 5-aminolevulinic acid-mediated sonodynamic therapy is the mitochondria-caspase pathway despite the participation of endoplasmic reticulum stress. Cell Physiol Biochem 33:1789–1801

    Article  CAS  PubMed  Google Scholar 

  103. Wang S, Hu Z, Wang X, Gu C, Gao Z, Cao W et al (2014) 5-Aminolevulinic acid-mediated sonodynamic therapy reverses macrophage and dendritic cell passivity in murine melanoma xenografts. Ultrasound Med Biol 40:2125–2133

    Article  PubMed  Google Scholar 

  104. Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA et al (2013) Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity 38:225–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Yi JS, Holbrook BC, Michalek RD, Laniewski NG, Grayson JM (2006) Electron transport complex I is required for CD8+ T cell function. J Immunol 177:852–862

    Article  CAS  PubMed  Google Scholar 

  106. Laniewski NG, Grayson JM (2004) Antioxidant treatment reduces expansion and contraction of antigen-specific CD8+ T cells during primary but not secondary viral infection. J Virol 78:11246–11257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Chaudhri G, Clark IA, Hunt NH, Cowden WB, Ceredig R (1986) Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation. J Immunol 137:2646–2652

    CAS  PubMed  Google Scholar 

  108. Schwindling C, Quintana A, Krause E, Hoth M (2010) Mitochondria positioning controls local calcium influx in T cells. J Immunol 184:184–190

    Article  CAS  PubMed  Google Scholar 

  109. Hehner SP, Breitkreutz R, Shubinsky G, Unsoeld H, Schulze-Osthoff K, Schmitz ML et al (2000) Enhancement of T cell receptor signaling by a mild oxidative shift in the intracellular thiol pool. J Immunol 165:4319–4328

    Article  CAS  PubMed  Google Scholar 

  110. Uzhachenko R, Ivanov SV, Yarbrough WG, Shanker A, Medzhitov R, Ivanova AV (2014) Fus1/Tusc2 is a novel regulator of mitochondrial calcium handling, Ca2+-coupled mitochondrial processes, and Ca2+-dependent NFAT and NF-kappaB pathways in CD4+ T cells. Antioxid Redox Signal 20:1533–1547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Tkachev V, Goodell S, Opipari AW, Hao LY, Franchi L, Glick GD et al (2015) Programmed death-1 controls T cell survival by regulating oxidative metabolism. J Immunol 194:5789–5800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Lysechko TL, Cheung SM, Ostergaard HL (2010) Regulation of the tyrosine kinase Pyk2 by calcium is through production of reactive oxygen species in cytotoxic T lymphocytes. J Biol Chem 285:31174–31184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Aguilo JI, Anel A, Catalan E, Sebastian A, Acin-Perez R, Naval J et al (2010) Granzyme B of cytotoxic T cells induces extramitochondrial reactive oxygen species production via caspase-dependent NADPH oxidase activation. Immunol Cell Biol 88:545–554

    Article  CAS  PubMed  Google Scholar 

  114. Murphy MP, Siegel RM (2013) Mitochondrial ROS fire up T cell activation. Immunity 38:201–202

    Article  CAS  PubMed  Google Scholar 

  115. Gelderman KA, Hultqvist M, Holmberg J, Olofsson P, Holmdahl R (2006) T cell surface redox levels determine T cell reactivity and arthritis susceptibility. Proc Natl Acad Sci U S A 103:12831–12836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Cemerski S, Cantagrel A, Van Meerwijk JP, Romagnoli P (2002) Reactive oxygen species differentially affect T cell receptor-signaling pathways. J Biol Chem 277:19585–19593

    Article  CAS  PubMed  Google Scholar 

  117. Efimova O, Szankasi P, Kelley TW (2011) Ncf1 (p47phox) is essential for direct regulatory T cell mediated suppression of CD4+ effector T cells. PLoS One 6:e16013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Kraaij MD, Koekkoek KM, van der Kooij SW, Gelderman KA, van Kooten C (2013) Subsets of human type 2 macrophages show differential capacity to produce reactive oxygen species. Cell Immunol 284:1–8

    Article  CAS  PubMed  Google Scholar 

  119. Wei J, Zhang M, Zhou J (2015) Myeloid-derived suppressor cells in major depression patients suppress T cell responses through the production of reactive oxygen species. Psychiatry Res 228:695–701

    Article  CAS  PubMed  Google Scholar 

  120. Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L et al (2007) Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med 13:828–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Wang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L et al (2017) Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell 32:42–56

    Article  PubMed  CAS  Google Scholar 

  122. Shan M, Qin J, Jin F, Han X, Guan H, Li X et al (2017) Autophagy suppresses isoprenaline-induced M2 macrophage polarization via the ROS/ERK and mTOR signaling pathway. Free Radic Biol Med 110:432–443

  123. Magda D, Miller RA (2006) Motexafin gadolinium: a novel redox active drug for cancer therapy. Semin Cancer Biol 16:466–476

    Article  CAS  PubMed  Google Scholar 

  124. Ray T, Chakrabarti MK, Pal A (2016) Hemagglutinin protease secreted by V. cholerae induced apoptosis in breast cancer cells by ROS mediated intrinsic pathway and regresses tumor growth in mice model. Apoptosis 21:143–154

    Article  CAS  PubMed  Google Scholar 

  125. Pluchino LA, Choudhary S, Wang HC (2016) Reactive oxygen species-mediated synergistic and preferential induction of cell death and reduction of clonogenic resistance in breast cancer cells by combined cisplatin and FK228. Cancer Lett 381:124–132

    Article  CAS  PubMed  Google Scholar 

  126. Ao X, Nie P, Wu B, Xu W, Zhang T, Wang S et al (2016) Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3. Cell Death Dis 7:e2463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zhu J, Zou Z, Nie P, Kou X, Wu B, Wang S et al (2016) Downregulation of microRNA-27b-3p enhances tamoxifen resistance in breast cancer by increasing NR5A2 and CREB1 expression. Cell Death Dis 7:e2454

    Article  PubMed  PubMed Central  Google Scholar 

  128. Zhang LH, Yang AJ, Wang M, Liu W, Wang CY, Xie XF et al (2016) Enhanced autophagy reveals vulnerability of P-gp mediated epirubicin resistance in triple negative breast cancer cells. Apoptosis 21:473–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Ledoux S, Yang R, Friedlander G, Laouari D (2003) Glucose depletion enhances P-glycoprotein expression in hepatoma cells: role of endoplasmic reticulum stress response. Cancer Res 63:7284–7290

    CAS  PubMed  Google Scholar 

  130. Terada Y, Ogura J, Tsujimoto T, Kuwayama K, Koizumi T, Sasaki S et al (2014) Intestinal P-glycoprotein expression is multimodally regulated by intestinal ischemia-reperfusion. J Pharm Pharm Sci 17:266–276

    Article  PubMed  Google Scholar 

  131. Li L, Xu J, Min T, Huang W (2006) Up-regulation of P-glycoprotein expression by catalase via JNK activation in HepG2 cells. Redox Rep 11:173–178

    Article  PubMed  CAS  Google Scholar 

  132. Pandey V, Chaube B, Bhat MK (2011) Hyperglycemia regulates MDR-1, drug accumulation and ROS levels causing increased toxicity of carboplatin and 5-fluorouracil in MCF-7 cells. J Cell Biochem 112:2942–2952

    Article  CAS  PubMed  Google Scholar 

  133. Dayal R, Singh A, Pandey A, Mishra KP (2014) Reactive oxygen species as mediator of tumor radiosensitivity. J Cancer Res Ther 10:811–818

    Article  PubMed  Google Scholar 

  134. Yu S, Wang L, Cao Z, Gong D, Liang Q, Chen H et al (2017) Anticancer effect of Polyphyllin Iota in colorectal cancer cells through ROS-dependent autophagy and G2/M arrest mechanisms. Nat Prod Res 16:1–4

  135. Sun M, Pan D, Chen Y, Li Y, Gao K, Hu B (2017) Coroglaucigenin enhances the radiosensitivity of human lung cancer cells through Nrf2/ROS pathway. Oncotarget 8:32807–32820

    PubMed  PubMed Central  Google Scholar 

  136. Zhang G, Wang W, Yao C, Ren J, Zhang S, Han M (2017) Salinomycin overcomes radioresistance in nasopharyngeal carcinoma cells by inhibiting Nrf2 level and promoting ROS generation. Biomed Pharmacother 91:147–154

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (Nos. 81402187 and 81772803), the Ph. D Start-up Fund of Natural Science Foundation of Guangdong Province (No. 2014A030310505 to Z. Zou), the Foundation for Distinguished Young Talents in Higher Education of Guangdong (No. C1085229 to Z. Zou).

Author information

Authors and Affiliations

  1. MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China

    Zhengzhi Zou, Haocai Chang, Haolong Li & Songmao Wang

  2. Joint Laboratory of Laser Oncology with Cancer Center of Sun Yat-sen University, South China Normal University, Guangzhou, China

    Zhengzhi Zou

Authors
  1. Zhengzhi Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haocai Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haolong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Songmao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhengzhi Zou.

Ethics declarations

Conflict of interest

The authors declare no competing financial interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zou, Z., Chang, H., Li, H. et al. Induction of reactive oxygen species: an emerging approach for cancer therapy. Apoptosis 22, 1321–1335 (2017). https://doi.org/10.1007/s10495-017-1424-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-017-1424-9

Keywords

Search

Navigation