Skip to main content
SpringerLink
Log in

Redox-active nanoceria depolarize mitochondrial membrane of human colon cancer cells

  • Research Paper
  • Published:
Journal of Nanoparticle Research Aims and scope Submit manuscript

Abstract

Nanotherapeutics is emerging as a promising option to the various limitations and side effects associated with conventional chemotherapy. The present study investigates the cytotoxic effect of redox-active cerium oxide nanoparticles (nanoceria) on human colorectal adenocarcinoma-derived cell line (HCT 15). Exposure of these cells to nanoceria for 24 h with concentration ranging between 10 and 100 μM resulted in a significant reduction of cell viability in a dose-dependent manner. Further, at a concentration of 10 µM, nanoceria exhibited time-dependent cytotoxic effect when exposed to the cells for 24, 48, and 72 h. Upon treatment of the cells with nanoceria, reactive oxygen species (ROS) and lipid peroxidation which are indicators of oxidative stress and cytotoxicity increased significantly, in a dose-dependent manner. Nanoceria was also found to depolarize the mitochondrial membrane, thereby collapsing the membrane potential and leading to initiation of apoptosis. Scanning electron microscopic study of nanoceria-treated HCT 15 cells showed morphological changes and loss of filopodia and lamellipodia, indicating arrest of metastatic spread. Summarizing, when cultured HCT 15 cells are exposed to nanoceria, a dose-dependent cytotoxic effect mediated by ROS generation is observed.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Alili L, Sack M, Karakoti AS, Teuber S, Puschmann K, Hirst SM, Reilly CM, Zanger K, Stahl W, Das S, Seal S, Brenneisen P (2011) Combined cytotoxic and anti-invasive properties of redox-active nanoparticles in tumor-stroma interactions. Biomaterials 32:2918–2929

    Article  Google Scholar 

  • Alili L, Sack M, Montfort C, Giri S, Das S, Carroll KS, Zanger K, Seal S, Brenneisen P (2013) Downregulation of tumor growth and invasion by redox-active nanoparticles. Antioxid Redox Signal 19:765–778

    Article  Google Scholar 

  • Asati A, Santra S, Kaittanis C, Perez JM (2010) Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano 4:5321–5331

    Article  Google Scholar 

  • Barchi JJJ, Rittenhouse-Olson K, Svarovsky S (2007) Carbohydrate antigen-nanoparticle conjugates and uses there of as antimetastatic agents in treating cancer. US20070275007 A1

  • Bednarski MD, Guccione S, Li K (2009) Use of targeted cross-linked nanoparticles for in vivo gene delivery. US7514098 B2

  • Boulikas T (2003) Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes. US6511676 B1

  • Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 60:1615–1626

    Article  Google Scholar 

  • Chidambaram M, Manavalan R, Kathiresan K (2011) Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J Pharm Pharm Sci 14:67–77

    Google Scholar 

  • Cho K, Wang X, Nie S, Chen ZG, Shin DM (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14:1310–1316

    Article  Google Scholar 

  • Das M, Patil S, Bhargava N, Kang JF, Riedel LM, Seal S, Hickman JJ (2007) Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. Biomaterials 28:1918–1925

    Article  Google Scholar 

  • Das S, Dowding JM, Klump KE, McGinnis JF, Self W, Seal S (2013) Cerium oxide nanoparticles: applications and prospects in nanomedicine. Nanomedicine (Lond) 8:1483–1508

    Article  Google Scholar 

  • Dowding JM, Seal S, Self WT (2013) Cerium oxide nanoparticles accelerate the decay of peroxynitrite (ONOO). Drug Deliv Transl Res 3:375–379

    Article  Google Scholar 

  • Gelperina S, Kreuter J, Sabel BA, Schroeder U (2000) Use of drug-loaded nanoparticles for the treatment of cancers. WO2000074658 A1

  • Giri S, Karakoti A, Graham RP, Maguire JL, Reilly CM, Seal S, Rattan R, Shridhar V (2013) Nanoceria: a rare-earth nanoparticle as a novel anti-angiogenic therapeutic agent in ovarian cancer. PLoS ONE 8:e54578

    Article  Google Scholar 

  • Hanley C, Layne J, Punnoose A, Reddy KM, Coombs I, Coombs A, Feris K, Wingett D (2008) Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles. Nanotechnology 19:295103

    Article  Google Scholar 

  • Hassan EM (2002) Elemental nanoparticles of substantially water insoluble materials. US20020119916 A1

  • Heckert EG, Karakoti AS, Seal S, Self WT (2008a) The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials 29:2705–2709

    Article  Google Scholar 

  • Heckert EG, Seal S, Self WT (2008b) Fenton-like reaction catalyzed by the rare earth inner transition metal cerium. Environ Sci Technol 42:5014–5019

    Article  Google Scholar 

  • Kukowska-Latallo JF, Candido KA, Cao Z, Nigavekar SS, Majoros IJ, Thomas TP, Balogh LP, Khan MK, Baker JR Jr (2005) Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer Res 65:5317–5324

    Article  Google Scholar 

  • Kuroda S, Katsuyuki T, Kondo A., Ueda M, Senoo S, Iwabuki H. (2003) Therapeutic medicine for hepatic disease using protein hollow nanoparticle. JP2003286199

  • Kuroda S, Tanizawa K, Kondo A, Ueda M, Seno M, Okajima T (2004) Therapeutic drug using antibody-presenting hollow protein nanoparticles and hollow protein nanoparticles. EP1491210 A1

  • Lin W, Huang YW, Zhou XD, Ma Y (2006) Toxicity of cerium oxide nanoparticles in human lung cancer cells. Int J Toxicol 25(6):451–457

    Article  Google Scholar 

  • Meng L, Yang L, Zhao X, Zhang L, Zhu H, Liu C, Tan W (2012) Targeted delivery of chemotherapy agents using a liver cancer-specific aptamer. PLoS ONE 7:e33434

    Article  Google Scholar 

  • Michael B, Regis C, Annekathrin H, Helmuth M, Marc S, Gleb S, Sergei Z, Heidi Z (2003) Preparation and use of dna-polyelectrolyte nanoparticles for gene transfer. WO2003087384 A1

  • Petit PX, Lecoeur H, Zorn E, Dauguet C, Mignotte B, Gougeon ML (1995) Alterations in mitochondrial structure and function are early events of dexamethasone-induced thymocyte apoptosis. J Cell Biol 130:157–167

    Article  Google Scholar 

  • Pirmohamed T, Dowding JM, Singh S, Wasserman B, Heckert E, Karakoti AS, King JE, Seal S, Self WT (2010) Nanoceria exhibit redox state-dependent catalase mimetic activity. Chem Commun (Camb) 46:2736–2738

    Article  Google Scholar 

  • Praetorius NP, Mandal TK (2007) Engineered nanoparticles in cancer therapy. Recent Pat Drug Deliv Formula 1:37–51

    Article  Google Scholar 

  • Thevenot P, Cho J, Wavhal D, Timmons RB, Tang L (2008) Surface chemistry influences cancer killing effect of TiO2 nanoparticles. Nanomedicine 4:226–236

    Article  Google Scholar 

  • Venkatesan P, Das S, Krishnan MMR, Chakraborty C, Chaudhury K, Mandal M (2010) Effect of AEE788 and/or Celecoxib on colon cancer cell morphology using advanced microscopic techniques. Micron 41:247–256

    Article  Google Scholar 

  • Wang H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27:612–616

    Article  Google Scholar 

  • Wason MS, Colon J, Das S, Seal S, Turkson J, Zhao J, Baker CH (2012) Sensitization of pancreatic cancer cells to radiation by cerium oxide nanoparticle-induced ROS production. Nanomedicine 9:558–569

    Article  Google Scholar 

  • Xue Y, Luan QF, Yang D, Yao X, Zhou KB (2011) Direct evidence for hydroxyl radical scavenging activity of cerium oxide nanoparticles. J Phys Chem C 115:4433–4438

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, 721 302, West Bengal, India

    Saikat Kumar Jana, Priyanka Banerjee & Koel Chaudhury

  2. Advanced Materials Processing and Analysis Center, Nanoscience and Technology Center (NSTC), Mechanical, Materials and Aerospace Engineering (MMAE), University of Central Florida, Orlando, FL, 32816, USA

    Soumen Das & Sudipta Seal

Authors
  1. Saikat Kumar Jana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Priyanka Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Soumen Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sudipta Seal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Koel Chaudhury
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Koel Chaudhury.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jana, S.K., Banerjee, P., Das, S. et al. Redox-active nanoceria depolarize mitochondrial membrane of human colon cancer cells. J Nanopart Res 16, 2441 (2014). https://doi.org/10.1007/s11051-014-2441-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11051-014-2441-z

Keywords

Search

Navigation